Increased Weight of the Liver in Wistar Albino Rats with Induced,and Transplanted Ttlmors Eleanor H. Yeakel, Ph.D. (From the Wistar Institute o] Anatomy and Biology, Philadelphia 4, and the Department ol Anatomy, Hahnemann Medical College and Hospital, Philadelphia 2, Pa.) (Received for publication January 12, 1948) In a report on changes with age in the livers of Wistar albino rats (4), it was pointed out that the average weight of the livers of old (600 to 1,000 days) females with spontaneous tumors elsewhere in the body was significantly heavier than that of tumor-free old females, and of younger females of comparable body length. In old male rats, in which growths rarely occurred, there was no such increase in the average weight of the liver. Comparison of the weight of mammary gland tumors with the weight of the host's liver revealed no correlation, except that enlargement of the liver was found when the weight of the growth exceeded 30 gm. The work presented here was undertaken to determine whether the apparent influence of tumors on the weight of the liver, as indicated above, was confined to spontaneous growths and occurred only in females, and whether it was correlated with old age. TABLE I : PROCEDURE Male and female Wistar albino rats were used. The experimental animals bore subcutaneously either a transferred fibrosarcoma, or a primary tumor induced by injection of methylcholanthrene. The growths did not metastasize. The exact ages of the rats were not calculated, but none was older than 300 days at death. When the animal was killed, the body length from nose to anus was measured, and the subcutaneous tumor, the carcass without the tumor, and the liver, were weighed. The weight of the liver relative to body weight and to body length was calculated. Corresponding control values were taken from the 21 to 300 day old rats dissected for the study of aging (4). RESULTS The data for the experimental female animals are presented in Table I, and for the males, in Table II. The rats are listed in order of increasing WEIGHT OF TUIIOR AND OBSERVED AND RELATIVE WEIGHT OF THE LIVER IN FEMALES Body weight Body length, (less tumor), Rat mm. gin. 1 202 231 2 225 342 3 214 270 4 207 201 5 176 151 6 175 138 7 217 210 8 207 244 9* 143 81 10 196 222 11 188 174 12" 167 98 13 213 239 14 199 197 15 207 212 16 201 204 17 211 230 18 194 166 19 200 200 20 199 211 21 191 173 22 200 185 23 211 265 * Body length less than 180 mm. t Tumor inoculated, but failed to grow. Tumor weight, gin. Neg. t 2 5 6 10 13 27 32 36 40 46 60 60 61 62 71 71 81 84 89 95 111 123 Liver weight, gin. 8.65 10.78 9.39 9.30 7.53 7.04 9.28 12.94 5.26 11.29 9.58 7.72 12.60 12.06 14.28 11.58 19.12 11.32 10.64 13.37 11.69 11.98 14.38 Liver Liver B.L. 0.0428 0.0479 0.0439 0.0449 0.0428 0.0402 0.0428 0.0625 0.0368 0.0576 0.0510 0.0462 0.0592 0.0606 0.0690 0.0578 0.0906 0.0584 0.0534 0.0672 0.0612 0.0599 0.0681 B.Wt. 0.0374 0.0315 0.0348 0.0462 0.0499 0.0510 0.0442 0.0530 0.0650 0.0512 0.0550 0.0787 0.0527 0.0610 0.0673 0.0567 0.0831 0.0682 0.0534 0.0633 0.0676 0.0686 0.0542 392 Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1948 American Association for Cancer Research. Yeakel--Liver Weight Increase in Rats with Tumors tumor weight. The individual weights of the liver divided by the body length in control and experimental rats are plotted against the body length in the graphs. From Table I it may be seen that no consistent relationship existed between the weight of the tumor and the actual weight of the liver, or its weight relative to body weight. With the exception of two rats (marked with an asterisk), the liver values relative to body length were greater than 0.0500 when the tumors weighed more than 30 gm. Further growth of the tumor was not accompanied by a proportional increase in liver size. The graph for the females shows that the liver weights of animals with tumors under 30 gm. lay within the range established by the normal controls. The two rats with heavier tumors but normal relative liver weights were small animals, with body lengths less than 180 mm. The relative weights in the remaining female hosts were clearly higher than normal. Less clear-cut but similar results were found in male rats. The liver weights relative to body length were greater than 0.0500 when the tumors weighed more than .30 gm. in all but 4 of the experimental animals (Table II). Three of these were small animals, with body lengths less than 180 mm. In the graph it may be seen that while some livers were very heavy compared with control values, there is a considerable spread of the relative weights, and 393 overlapping with the control group. However, the average relative weight of the livers of tumor-bearing males (over 190 mm. body length) is 0.0632 ___ 0.0021, and of control males of the same range of body length, 0.0499 + 0.0010; the standard error of the difference between the means being 0.0023, the actual difference is significant statistically. DISCUSSION The results of this experiment extend the earlier observations (4) on old female rats with spontaneous tumors to include adult animals of both sexes with induced and transplanted neoplasms. The relationship between the presence of a tumor and an increase of liver weight is clearer, however, in female rats than in males. There are several interesting parallels with the results obtained by McEwen and Haven (1): (a) These authors, using young male rats inoculated subcutaneously with carcinosarcoma 256, found a significant increase in the percentage of water in the liver, providing the tumor exceeded a critical weight (10 gin.). (b) The percentage of water did not increase with further growth of the tumor. (c) The weight of the liver relative to body weight did not differ significantly from the control figures. In the calculations reported in the present paper, the use of body length rather than body weight as a measure of size revealed a relation between the TABLE I I : WEXGHT Or TUMOR AND OBSERVED AND RELATIVE WEIGHT OF THE LIVER IN MALES Rat 1 2 3 4 5 6* 7 8 9 10 11 12 13 14" 15" 16 17 18 19 20 21 22 23 24 25 26 Body length, ram. 176 165 162 216 221 172 180 217 216 204 213 185 220 171 159 211 228 221 198 202 194 205 206 215 226 219 Body weight (less tumor), gin. 133 110 293 288 311 131 197 293 255 220 264 217 332 129 89 246 327 293 206 194 189 224 206 282 319 245 Tumor weight, gin. 12 26 27 31 32 33 39 42 42 42 43 44 44 46 47 48 50 54 60 67 72 75 81 83 96 126 Liver weight, gin. 6.64 7.56 5.52 13.84 13.36 6.47 14.89 14.74 12.16 11.20 11.51 15.75 16.40 7.t9 4.93 12.05 15.62 14.07 9.09 11.76 11.57 13.85 13.07 17.81 16.59 14.22 Liver Liver B.L. 0.0377 0.0458 0.0341 0.0641 0.0605 0.0376 0.0827 0,0680 0.0563 0.0549 0.0540 0.0851 0.0745 0.0421 0.0310 0.0571 0.0685 0.0637 0.0459 0.0582 0.0597 0.0676 0.0634 0.0829 0.0734 0.0649 B.wt. 0.0499 0.0688 0.0594 0.0408 0.0430 0.0571 0.0756 0.0503 0.0477 0.0509 0.0436 0.0726 0.0494 0.0557 0.0548 0.0490 0.0477 0.0480 0.0441 0.0605 0.0612 0.0618 0.0634 0.0632 0.0520 0.0581 Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1948 American Association for Cancer Research. Cancer Research 394 .0900 FEMALES 0800 RA -wT -fu ORS- ~. .0700 OVER 30 GRAMS 9 -- CONTROL RATS .o6oo e e UNDER 3 0 GRAMS o _" 9 / e ~_ "4 9 _ / ILl _j .0500 .- "0/ //O" O e , ~000 9 ~ " 9 / L |.eO 00 " 9 " 9 ~ " ~ 1 ~ / M V ~ " . ~9Z . ~ -, A ,a~-~ d,,~ 0 m .0400 - - e/~ : I Q ~% ~ / 9 OOkO .0300 ~,'./ --3 9 " .0200 9 .0100 ~ I00 9 I I I I ! I 120 140 160 180 200 220 BODY LENGTH [MM.) FIo. 1.--Relation of relative liver weight to the body length in females. Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1948 American Association for Cancer Research. Yeakel,----Liver Weight Increase in Rats with Tumors .0900 395 D MALES 9 9 .0800 .0700 -- :0600 -~ .o5oo __ OVER 30 GRAMS 9 , UNDER 30 GRAMS o 9 CONTROL RATS 9 ~ __ e/ 9 9 - / - / 9 /'~ .o'/,,,,". .0400 / 9 ../ 9 /k% 9 9 ~ 9 9 f" -"X'" O ~ ". -:.2,,::,,, , 9 ,,'q, " ".- 9 .., .0300 > @, -5 /'. .0200 .0100 I 100 120 14.0 160 I 180 200 2 20 BODY LENGTH CMM.) FIG. L--Relation of relative liver weight to the body length in males. Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1948 American Association for Cancer Research. 396 Cancer Research liver and the presence of a tumor in rats over 175 ram., although the effect on the liver was not apparent in smaller (younger) rats. Constituents of the liver other than water may influence the weight of this organ. Glycogen and fat, as pointed out by Walter and Addis (3), represent passive reserve material, while an increase in protein content, they believe, reflects work performed by the organ. In pregnancy (2, 3), the weight of the liver as well as the percentage of total body protein in it is increased. Addis and his colleagues consider that this indicates a work hypertrophy, connected probably with protein anabolism. It is possible that similar work on the part of the liver concomitant with the synthesis of neoplastic tissue may account for the increase in the weight of the organ reported here. Moreover, the failure to find an enlargement of the liver (compared with the controls) in smaller, younger rats less than 180 ram. in body length may be explained by the supposition that these animals were still engaged in rapid body growth, so that their livers w e r e already enlarged to the physiological maximum, and the additional stress imposed by a tumor produced no demonstrable effect upon the liver weight. SUMMARY 1. The weight of tumor-free livers of male and female Wistar albino rats with subcutaneous growths (transplanted or primary) was compared with the weight of the tumor. 2. Neither the observed weight of the liver, nor its weight relative to the body weight (without the growth) was correlated with the tumor weight. 3. The weight of the organ relative to body length was significantly increased when the tumor weighed over 30 gin. and when the body length of the rat was over 175 mm. 4. Further growth of the tumor was not accompanied by a proportional increase in liver size. 5. The influence of a tumor on the weight of the host's liver was more evident in female rats than in males. 6. It is suggested that the enlargement of the liver was connected with protein anabolism in t h e growth of the tumor. ACKNOWLEDGMENT The author is deeply indebted to Dr. Margaret Reed Lewis oi the Wistar Institute, Philadelphia, for the use of her rats, and her advice and direction in this work; and to Dr. Henry S. Simms, of the Department of Pathology, College of Physicians and Surgeons, New York, for advice in the preparation of the manuscript. REFERENCES 1. McEw~, H. D., and HAVF~, F. L. The Effect of Carcinosarcoma 256 on the Water Content of the Liver. Cancer Research, 1:148-150. 1941. 2. Poo, L. J., LEw, W., LF~, D. D., and AVDIS,T. Protein Anaboilsm in the Organs and Tissues of Pregnant Rats at Different Levels of Protein Consumption. J. Nutrition, 19:505-516. 1940. 3. WALTTm, F., and ADVIS, T. Organ Work and Organ Weight. J. Exper. Med., 69:467-483. 1939. 4. YF~x~J~, E. H., and FARRm, E. J. Changes with Age in the Weight of the Liver in Wistar Albino Rats. Anat. Rec., 97:377-378 (Abstract). 1947. .iLDICAL TECta,, ! Ak Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1948 American Association for Cancer Research. Increased Weight of the Liver in Wistar Albino Rats with Induced and Transplanted Tumors Eleanor H. Yeakel Cancer Res 1948;8:392-396. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/8/8/392.citation Sign up to receive free email-alerts related to this article or journal. 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