Regeneration of Hair Follicles and Sebaceous Glands from the Epithelium of Scars in the Rabbit* CHARLESBREEDIS (Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pa.) It has been generally accepted that, when all the hair follicles and sebaceous glands in a region of adult skin are destroyed, or the entire region is extirpated, the new epithelium growing in from the side will not regenerate these structures (14). On the basis of this concept, attempts were made to obtain a purely squamous sheet of epi thelium in the rabbit for the purpose of inoculating it with the Shope papilloma virus. A region of skin was surgically removed from the back, and the wound was allowed to heal under conditions that largely prevented contraction and drying. Con trary to expectation, functioning hair follicles and sebaceous glands appeared in the scars, sometimes in great profusion. In the experiments here reported, wounds in various stages of healing were studied in an at tempt to determine the origin of the new hair follicles and glands. The "hair follicle" is here considered a purely epithelial derivative, by Ham (6). as defined by Cowdry (3) and MATERIALS AND METHODS Rabbits of mixed breeds weighing 2,800-3,500 gm. were used. They were fed commercial rabbit pellets, supplemented in some experiments with greens. All operations described below were performed under Nembutal anesthesia and as aseptically as possible. To obtain a uniform and large sheet of scar epithelium it was thought desirable to hinder as much as possible the con traction of the wound during healing. For this purpose a wire ring was devised that could be anchored in the skin surrounding the wound. The ring consisted of a 22-gauge surgical stainless steel wire bent into the form shown in Figure 1 (C). The ring was fastened in the skin as follows : The back of the rabbit was shaved with an electric clipper and was depilated with a mixture of equal parts of barium sulfide and cornstarch made to a thin paste with water. The ring was placed on the middle region of the back, 2 or 8 cm. from the midline. Its outline was traced with India ink, thus forming a circle on the skin 33 mm. in diameter. The positions of the seven prongs were marked on the circle. The ring was then sterilized by *This investigation was supported by a research grant (C-1116) from the National Cancer Institute of the National Institutes of Health, Public Health Service. Received for publication April 21, 1954. boiling, during which time the skin was painted with iodine and then washed with ether. A disc of skin about 25 mm. in diame ter was cut with a scissors from within the circle of ink and con centric with it. The disc included the total thickness of skin as well as the underlying panniculus carnosus. The wire ring was now pushed through the wound into the subcutaneous tissue and was so placed that its upward pro jecting prongs coincided with the marks on the India ink circle. The skin was punctured at each mark with a No. 11 Bard-Parker blade, thus allowing the prongs to project through the skin. The appearance of the anchor ring in relation to a healed wound is shown in Figure 3. The wound was protected by a glass-covered chamber fastened to the ring, as shown in Figure 2. The chamber con sisted of a heavy stainless steel ring with three projecting lugs (Fig. 1 [B]) and an ordinary chemical watch glass (Fig. 1 [A]). The under surface of the ring had a shallow groove into which the seven prongs of the underlying wire ring were fitted. The heavy ring, placed on top of the prongs, was firmly attached to each with 28-gauge stainless steel wire. The glass cover was then fastened in place, as shown in Figure 2, with 25-gauge stainless steel wire. The chamber was left in place, except for temporary re moval of the glass cover when observations were made or dressings applied, until the end of the experiment. Then the animals were sacrificed with Nembutal. For microscopic examination sections were cut perpendicular to the skin sur face after fixation in Bouin's solution. Whole mounts of the epithelium were prepared by the acetic acid method described by Cowdry (4). Only the epithelium of the scar separated readily by this method. Mature hair follicles in the surround ing skin were too deep to be pulled out. The best results were obtained by soaking in ice-cold 1 per cent acetic acid for 2-3 days, fixing in Bouin's solution for 1 day at room tempera ture, and then lifting off the scar epithelium. Preparations of the dermal papillae were made after re moving the epithelium. Using a razor blade, a thin slice of the dermal surface was shaved off and stained with hematoxy lin. EXPERIMENTAL RESULTS Dressing of the wound and rate of healing.—In the first five rabbits the wound was kept moist with vaseline gauze dressings. With this treatment the wound did not develop a base that moved with the skin, but remained open to the subcutaneous tissue until granulation from the side closed the defect. The closure required 18-30 days and com plete epithelialization several additional days. Three of the wounds became infected. Leaving the wound alone resulted in more rapid 575 Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. 576 h. F" Cancer Research healing and only an occasional infection. This pro cedure was adopted for the remaining 33 animals. The chamber allowed slow evaporation to occur, and the wound healed by scab formation and granulation. The sequence of events was as follows : As dry ing proceeded, the upper layer of the loose sub cutaneous tissue became attached to the edges of the wound and moved with the skin. In 7-10 days this membrane became thick and opaque. In 10-14 days a brown scab covered the entire wound. The granulation tissue growing in from the side reached the center in 15-22 days. Epithelialization was usually complete several days thereafter, and the scab separated. Beginning at about the time of separation of the scab or several days before this occurred, vaseline gauze dressings were applied every 3-6 days. When the new epithelium was not protected in this way, and especially when the glass cover was left off the chamber, there was excessive drying and contraction of the wound with little or no regeneration of hair follicles and sebaceous glands. Organization of the scar epithelium into hair fol licles and sebaceous glands.—Microscopic observa tions were made on sections through the wounds from 23 rabbits and on whole epidermal mounts from fifteen additional rabbits. None of the sections showed evidence that hair follicles or sebaceous glands had been left within the wound area at the time of operation. All epi thelium either was confined to the surface of the granulation tissue or appeared to be projecting from this surface epithelium into the granulation tissue. Sections of wounds not yet completely epithelialized showed scattered diffuse thickenings of the epithelium. These are illustrated in Figure 4, which represents a wound of 23 days. The thick ened epithelium consisted of five or more layers of cuboidal cells and showed no evidence of organiza tion. At about 30 days, when epithelialization was usually complete, the thickened regions developed downward projections into the granulation tissue. Some of these could be identified as early hair fol licles. Such a follicle is shown in Figure 5. Between 32 and 40 days, functioning hair follicles appeared and were sometimes present in great numbers, as illustrated in Figure 6. Once organization and growth of the follicles had begun, they penetrated rapidly into the granulation tissue. In wounds of 45-55 days many of the new follicles were as deep as those of the normal skin at the edge of the wound. While these observations suggested a true re generation of follicles from the surface epithe lium, there were other possible explanations. The trauma of making the wound and of affixing the chamber may have loosened viable fragments of hair follicles, which could either be scattered over the wound or be carried into it by the migrating surface epithelium. Some parts of a follicle can regenerate the whole (6). To determine the distribution of the new fol licles and to study their structure in three dimen sions, whole mounts of the wound epithelium were made as described above. Mounts prepared at various stages of healing revealed the following sequence of events : Before the epithelium had completely covered the wound it had numerous bands or bars of thickening that consisted of five or more layers of cuboidal cells. Most of them were radially arranged, but many formed a reticular pattern that connected with the radial bars. This arrangement is illustrated in Fig ure 7 (27 days). The bars correspond to the thick enings of epithelium shown in cross-section in Fig ure 4. No organized structure could be seen in them. Some of the bars could be traced back to hair follicles at the edge of the wound. As epithelialization proceeded, most of the con necting bars disappeared while the radial ones per sisted. Then numerous budlike projections ap peared on the bars, first at the periphery of the wound and later near the center. This budding is illustrated in Figures 8 and 9 (31 days). Each bud was an immature hair follicle that in cross section would appear about as shown in Figure 5. Sometimes the radial bars could be seen through the dissecting microscope in the living animal. Radially arranged blood vessels were also some times seen under the wound epithelium. As the hair follicles matured and began to pro duce hair, the radial bars gradually disappeared, leaving radially arranged rows of follicles. These rows are seen at the periphery of the scar in Figure 8 (31 days) and near its center in Figure 10 (33 days). Still later, owing perhaps to local contrac tions of the healing wounds, the linear arrange ment disappeared entirely, as illustrated in Figure 11 (50 days). It is of interest that in epidermal mounts pre pared from four rabbit embryos (3 weeks), the hair follicles arose as discrete thickenings of the epiderm, arranged in a geometrical pattern. There was no evidence of thickened epidermal bars. The sebaceous gland, in the region of skin under consideration, is a derivative of the hair follicle and is always associated with it. Sections do not show it well unless the cut is through both the gland and the follicle. Figure 15 (50 days) illustrates such a gland adjacent to a regenerated follicle in a rabbit Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. BREEDIS—Regeneration of Hair Follicles and Sebaceous Glands that had also been inoculated with the Shope papilloma virus. In the epithelial mounts the se baceous gland appears as a bulbous swelling of the neck of the follicle near its attachment to the sur face epithelium (Fig. 12). The sebaceous gland was first noted at about the time the follicle began to produce hair. The role of dermal elements in the regeneration of hair follicles.—The arrangement of the hair fol licles in the epithelial mounts and their budding from otherwise unorganized epithelial bars argued strongly against a possible random seeding of the wound by hair follicle fragments. The chances against repeated occurrence of the radial pattern would be enormous. However, the influence of an other factor, dermis, had to be considered. The hair follicle is in intimate contact with dermal structures, perhaps the most important of which is the dermal papilla. The papilla lies inside a cup-shaped excavation in the bulb of the hair fol licle. Several are well shown in Figure 12. In the embryo the papilla is thought to "induce" the hair follicle (1, 7). Had dermal elements induced the hair follicles in the regenerating skin? If so, how had this come about? Preparations of the entire dermal surface under lying the scar epithelium were made as described above. Six healed wounds varying from 31 to 50 days in age were examined. In each case the epi thelium, which had been removed as a single sheet, was also available for study. The 31-day preparation of dermal surface was that underlying the epithelium shown in Figure 8. As seen from this figure, hair follicles were just be ginning to bud from the central portions of the epithelial bars and were already fairly well or ganized at the periphery. On examining the dermal surface under this epithelium, the radial grooves left by the epithelial bars were visible, and also the depressions left by the buds. Condensations of cells that might be early dermal papillae were made out with some difficulty along the grooves in the cen tral parts of the wound. Unquestionable early der mal papillae were seen near the periphery of the wound, under the more advanced hair follicles. Figure 13 illustrates the appearance of these early papillae. The later preparations (34-50 days) showed an increase in size and organization of the papillae that paralleled the development of the hair fol licles. The mature papillae stained densely with hematoxylin and were clearly visible at the bottom of the holes from which the hair follicles had been pulled. Figure 14 illustrates their appearance in the 50-day preparation. In all six dermal preparations the papillae were 577 always associated with hair follicles, and, con versely, epithelial buds that could be identified as hair follicles always had under them dermal papil lae. Hence, it could not be determined whether or not one structure induced the other. Both ap peared at about the same time and increased in size together. Regeneration of hair follicles in scars inoculated with the Shope papilloma virus.—The wounds of five rabbits were inoculated with the Shope papil loma virus at 21, 32, 33, 35, and 41 days, respec tively, after removal of the disc of skin. The virus suspension was inoculated over a narrow band of skin and scar that extended anteroposteriorly across the entire inside diameter of the chamber. The animals were sacrificed 12-15 days after in oculation. All the animals developed typical papillomas involving the scar epithelium, and all bore evi dence of regeneration of hair follicles and seba ceous glands from this epithelium. The virus ap parently did not interfere with the regeneration. Cells of the papilloma merged with hair follicle epithelium as well as with epithelium between fol licles, and it could not be determined from what cell type the papilloma had arisen (see Fig. 15). DISCUSSION The question of whether the epidermis can give rise to new hair follicles in the adult has been ar gued since the time of O. Hertwig (8). One of the most prominent recent investigators to support the "new formation" hypothesis is Lacassagne (10), who has reported the redifferentiation of hair follicles and sebaceous glands in the scars of ultra violet-ray burns of mice. However, the opposite opinion is so universally held that, for example, one reviewer (11) has questioned the accuracy of a histological study in its entirety because the au thors mentioned the development of new hair fol licles in scars following the total extirpation of a region of skin (5). Evidence in the literature of the origin of new hair follicles has been scanty or absent. Their de velopment has been difficult to observe because of their sporadic occurrence. In the present experi ments such observation was possible only because the hair follicles regenerated fairly consistently and often in profusion. The conditions that determine whether regener ation of hair follicles will take place are not en tirely clear. At least the following factors seem to be involved: (a) Prevention of excessive drying and contraction of the wound appear to be impor tant, since the best regeneration, in the present experiments, occurred in wounds where these fac- Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. 578 Cancer Research tors were controlled. (6) The phase of the hair growth cycle may have an effect, although accord ing to Roney et al. (15) injury at once initiates growth of resting follicles in the rabbit, (c) Another important factor is the "granulation tissue" which fills the skin defect, especially that part of it which comes to lie immediately under the epithelium. It is generally assumed that in the embryo certain elements of the dermis induce the hair follicle (1, 7). In the present experiments these elements would be derived from the dermis at the edge of the wound and would come to lie in the indifferent granulation tissue that eventually fills the wound. To induce hair follicles in the overlying epithelium they would presumably have to lie immediately under this epithelium. The importance of the dermal papilla in the maintenance of the hair follicle throughout its cycles of activity has been emphasized by Chase (2). However, some differentiation of follicle epi thelium into highly specialized cells can occur in its absence. Montagna et al. (13) studied mice with hereditary hairlessness, which lose their ability to produce hair early in life. The hair follicle under goes a degenerative beadlike constriction in its middle portion, with eventual separation of the bulb from the remainder of the follicle. The iso lated external sheath cells then differentiate into sebaceous gland cells. On the other hand, Mon tagna and Chase (12) found in normal mice that, while sebaceous glands regenerated from external sheath cells after the former were destroyed by methylcholanthrene, this regeneration did not be gin until the follicle began to produce hair. Appar ently, the normal hair follicle and papilla act to gether to prevent excessive differentiations and to integrate the ones that occur. The regeneration of skin described in the pres ent experiments is comparable to the regeneration of the amphibian limb. The limb blastema (14) is derived from the amputation stump and is com posed of undifferentiated epidermal and deeper cells. Cells of the blastema subsequently differenti ate into various tissue cells of the new limb. The "skin blastema," similarly, is composed of undif ferentiated epidermal and dermal cells. Both are derived from the edges of the wound, and both subsequently undergo differentiation and organi zation. The experiment with the Shope papilloma virus was performed before it was found that hair fol licles could regenerate. It was hoped that scars would yield a uniform and hairless epiderm on which to induce papillomas for an electron micro scopic comparison of the papilloma cell and its nor mal precursor. However, none of the five scars on which the virus was inoculated turned out to be free of hair follicles. Kidd and Parsons (9) tested the virus on a variety of epithelial surfaces and found that it induced papillomas only on skin, in areas that contained hair, although their results are not stated in exactly this way. Hair follicles and sebaceous glands are impor tant in epidermal carcinogenesis. Simpson and Cramer (16) showed that methylcholanthrene con centrates in the sebaceous glands. Lacassagne and Latarget (10) applied methylcholanthrene to scars of ultraviolet-ray burns of mice and found cancers in regions only where there were persisting, or re generated, hair follicles and glands. Suntzeff et al. (17) showed that methylcholanthrene applied to the skin of young mice before the hair follicles and sebaceous glands had fully developed failed to pro duce cancer. The role of the regenerative proper ties of skin in carcinogenesis remains to be deter mined. SUMMARY Discs of skin of total skin thickness were re moved from the backs of rabbits. The wounds were hindered from contracting and excessive drying by means of a protective chamber and were allowed to heal by scab formation and granulation. Functioning hair follicles and sebaceous glands developed in the scars, sometimes in great pro fusion. It was shown that these structures arose by Fio. 1.—The parts of the chamber used to protect the wounds and hinder them from contracting (see text). XI. Fio. 2.—Chamber in place over a healed wound. The skin was depilated just before the photograph was taken. X1. Fio. 8.—Samewound as in Figure 2, with parts A and B of chamber removed. The outlines of the scar are not distinct because of extensive regeneration of hair follicles. X1.4. Fio. 4.—Healing wound at 28 days. The epithelium has not yet reached the center of the wound, which is at the extreme left of the photograph. Note the irregular thickenings of the epithelium. These thickenings correspond to the radial bars shown in Figure 7. Hematoxylin and eosin. X14. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. *- 2 Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. FIG. 5.—Central part of wound at 32 days. The downward projecting epithelial process at the left is a beginning hair follicle. Hetnatoxylin and eosin. X105. FIG. 6.—Samewound as in Figure 5 hut a region halfway between the center and periphery of the wound. The hair follicles have penetrated deeply into the granulation tissue and are producing fine hairs. Hematoxylin and cositi. X105. FIG. 7.—Wholemount of the epithelium that partly covers a healing wound at 27 days, as seen from below. The unepithelialized center <ifthe wound is at the upper right. Note the bars of thickened epithelium, most of them radially arranged. Hematoxylin. X14. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. -, ^.-v"'*-<. _-^ïA><Ts. »5C>^ . ""k ' 'ì i*" ««S* ' \. ^ ' ... - .--o- •(. •«-"* ^ 1W Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. Fio. 8.—Whole epithelial mount of a healed wound at 31 «lays,as seen from below. The large white area is an artifact, the epithelium having failed to separate from the underlying granulation tissue in this region. Hair follicles are Imdding from the radially arranged epithelial bars. They are more advanced near the periphery than near the center. Hematoxylin. X14. FIG. 9.—Same preparation as shown in Figure 8 but at higher magnification. The cup-shaped depressions in the hair follicle buds are clearly visitile. These depressions contain the dermal papillae, which are left with the underlying dermis when the epithelium is pulled off. Hematoxylin. X105. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. „,? m^&ï* V\* Ti"*V * \^r./. ~;,^«::V':*4^- '••;,"-'-/ • if ** f «-18£<¿-* »r* A- // -,.;, s .-v'-'j * ^- '•i , * * V-«-^ * + ^ + •••"•^';' .-ff ** »- ^ /-r Jjrjß. ' ^<^-«*, ' . « 9 Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. FIG. 10.—Wholeepithelial mount of a healed wound at 33 days. The large oval defect near the top of the photograph is an artifact. The epithelial Imrs from which the hair follicles developed have largely disappeared, hut their linear arrange ment is still present near the center. The large coarse hairs at the lower right- and lower left-hand corners are not derived from the wound epithelium hut from follicles at the margin of the wound. Hematoxylin. X14. FIG. 11.—Wholeepithelial mount of a healed wound at 50 days. The epithelial hars and the linear arrangement of the hair follicles have now disappeared. Many of the follicles had grown so deeply into the regenerated dermis that their deeper parts did not pull out when the epithelium was removed, and so only their upper portion is present. These appear in the photograph as short, empty cylinders attached to the epi thelial sheet. The intact follicles have a densely staining bulb, and a hair is growing from each. For some reason the conditions for regeneration were not good near (lie periphery of this wound, as most of the new follicles are in the more cen tral regions. Hematoxylin. X14. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. 11 Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. FIG. 12.—Wholeepithelial mount of ¡ihealed wound at 35 days. The epithelial bars from which the hair follicles arose are still present but are disappearing. The bulbs of the follicle.«, which contain the dermal papillae, are clearly visible. The follicles are producili}; fine hairs, which are seen going out of focus toward the surface of the scar. The sebaceous glands are the bulbous swellings on the necks of the hair follicles near their attachment to the surface epithelium of the scar. Hematoxylin. X105. FIG. 13.—Surface of the regenerating dermis underlying the epithelium shown in Figures 8 and 9. The densely staining oval structures are the young dermal papillae. They are seen best near the center of the photograph. Ilematoxylin. X 105. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. FIG. 14.—Surfaceof the dermis underlying the epithelium shown in Figure 11 (5(1days). The dermul papillae are the large, densely staining oval structures. They lie in the holes left in the dermis when the hair follicles were pulled out. Note the increase in size over the early papillae shown in Figure 13. Hematoxylin. X105. FIG. 15.—Sectionthrough a healed wound that had heen inoculated with the Shope papilloma virus. The papilloma surrounds a hair follicle. On the left side of the hair follicle there is a sebaceous gland. Hematoxylin and eosin. X105. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. v 14 15 Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. BREEDIS—Regenerationof Hair Follicles and Sebaceous Glands budding from radially arranged bars of thickened epithelium, at least some of which had grown or migrated from cut hair follicles at the edge of the wound. The dermal papillae formed at about the time of budding of the hair follicles and developed together with them. The Shope virus induced papillomas on the re generating skin, but their cell of origin could not be determined. It is concluded that scar epithelium, under the conditions of the experiments, is capable of redifferentiating into hair follicles and sebaceous glands and that "granulation tissue" of the scar is capable of redifferentiating into dermal papillae. ACKNOWLEDGMENTS The author wishes to thank Dr. William Montagna and Dr. Herman B. Chase of the Department of Biology, Brown Uni versity, for their critical examination of some of the microscopic preparations and for helpful suggestions. REFERENCES 1. BÃœTCHEB, E. O. Development of the Pilary System and the Replacement of Hair in Mammals. Ann. N.Y. Acad. Sc., 63:508-16, 1951. 2. CHASE,H. B. Growth of the Hair. Physiol. Rev., 34:11326, 1954. 3. COWDBT,E. V. A Textbook of Histology, p. 554. 4th ed. Philadelphia: Lea & Febiger, 1950. 4. . Laboratory Technique in Biology and Medicine, p. 118. 3d ed. Baltimore: Williams & Wilkins, 1952. 5. DANN,L.; GLÃœCHSMAN, A., and TANSLEY,K. The Healing of Untreated Experimental Wounds. Brit. J. Exper. Path., 22:1-9, 1941. 579 6. HAM,A. W. Histology. 2d ed. Philadelphia: J. B. Lippincott, 1953. 7. HARDY,M. H. The Development of Pelage Hairs and Vibrissae from Skin in Tissue Culture. Ann. N.Y. Acad. Sc., 63: 546-61, 1951. 8. HEHTWIG,0. Textbook of the Embryology of Man and of Mammals, p. 526. Translated from 3d German edition. London: Swan Sonnenshein & Co.; New York: Macmillan Co., 1901. 9. KiHD,J. G., and PASSONS,R. J. Tissue Affinity of Shope Papilloma Virus. Proc. Soc. Exper. Biol. & Med., 35:43841, 1936. 10. LACASSAONE, A., and LATARGET,R. Methylcholanthrene on Certain Scars of the Skin in Mice. Cancer Research, 6:183-88, 1946. 11. LINDQUIST,G. The Healing of Skin Defects. An Experi mental Study on the White Rat. Acta Chirurg. Scandinav., 94 (suppl. 107): 1-163, 1946. 12. MONTAGNA,W., and CHASE,H. B. Redifferentiation of Sebaceous Glands in the Mouse after Total Extirpation with Methylcholanthrene. Anat. Ree., 107:83-92, 1950. 13. MONTAGNA,W.; CHASE,H. B.; and MELABAGNO, H. P. The Skin of Hairless Mice. I. The Formation of Cysts and the Distribution of Lipids. J. Invest. Dermatol., 19:83-94, 1952. 14. NEEDHAM,A. E. Regeneration and Wound-healing, p. 12. London: Methuen & Co.; New York: John Wiley & Sons, 1952. 15. RONET, H. R.; COHEN,D. M.; and SCHAFFNER,I. Pat terns of Hair Growth Cycles in the Colored Rabbit and Their Modification by Experimental Means. J. Invest. Dermatol., 21:313-30, 1953. 16. SIMPSON,W. L., and CRAMER,W. Fluorescence Studies of Carcinogens in Skin. I. Histological Localization of 20Methylcholanthrene in Mouse Skin after a Single Applica tion. Cancer Research, 3:362-69, 1943. 17. SUNTZEFF,V.; CAHRUTHEHS, C.; and COWDRY,E. V. The Role of Sebaceous Glands and Hair Follicles in Epidermal Carcinogenesis. Cancer Research, 7:439-43, 1947. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research. Regeneration of Hair Follicles and Sebaceous Glands from the Epithelium of Scars in the Rabbit Charles Breedis Cancer Res 1954;14:575-579. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/14/8/575 Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected]. Downloaded from cancerres.aacrjournals.org on June 14, 2017. © 1954 American Association for Cancer Research.
© Copyright 2025 Paperzz