ANN IST SUPER SANITÀ 2006 | VOL. 42, NO. 2: 109-112 Preface “Basic research must continue. It is clear that a better understanding of what happens in the malignant transformation will improve both therapy and prevention of cancer. The treatment of sick people is an urgent necessity; patients do not have time to waste. But why to focus only on therapy and to ignore primary prevention? (...) Primary prevention is not particularly lucrative; it limits profit and is not a good basis for financial speculation. It should be able to count on basic research to unmask the hypocrisy that obtructs its implementation, but too few researchers devote themselves to it. A majority of investigators is attracted, and distracted, by priorities dictated by the economic power with more generous and accessible financement channels and favourable chances of being published in prestigious scientific journals. Research on primary prevention has always been poor.” Renzo Tomatis. Il fuoriuscito. Milano: Sironi Editore; 2005. This volume is dedicated to the memory of Professor Romano Zito, director of research emeritus at the Regina Elena Institute for Cancer Research. Professor Zito died on Saturday February the 5th, 2005, at his home, at the age of 73, after many years of painful and courageous struggle against a tumour of the bladder, probably caused by heavy exposure to various chemicals in the earlier years of his laboratory work. The selected topic and articles published here refer to a research area “Environmental carcinogens and primary prevention” of great interest for him. He made some very important experimental and theoretical contributions in this area, showing outstanding competence and high ethical and professional integrity. The choice of Annali dell’Istituto Superiore di Sanità, the Annals of the Italian National Institute of Health (ISS) is to remember with respect and gratitude his continuous, voluntary assistance to the ISS experimental and advising activity in the field of carcinogenesis. The articles prepared by the Authors, most of which belong to the ISS, refer to some themes of primary cancer prevention, in which Professor Zito was deeply involved, offering his precious and often decisive collaboration. His continuous and generous efforts in favour of primary cancer prevention rather than secondary or tertiary prevention, i.e. the elimination of carcinogenic agents or the drastic reduction of human exposure to them, should not go unforgotten. His death has left a feeling of great loss and sorrow not only in the staff of the ISS, but also in the entire scientific community. Angelo Carere Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy 109 110 ANN IST SUPER SANITÀ 2006 | VOL. 42, NO. 109-112 In Memoriam Romano Zito, son of a famous clinical pathologist, studied medicine at the University “La Sapienza” of Rome, graduating in 1956 with an experimental thesis entitled “Physico-chemical aspects and chemical structure of myeloma’s seroalbumin”. During the university studies he worked at the Laboratory of Pathological Anatomy of the Istituto Regina Elena of Rome (Institute for Cancer Research) for 18 months (1951-52), learning pathology and conducting histochemical investigations on the tumour necrosis. Strongly attracted by the scientific research and in particular by chemistry and biochemistry, in 1952 he moved to the scientific division of the Regina Elena Institute. There, he started a long and fruitful collaboration with Professor Denis Kertész with studies on the purification and properties of the enzyme phenol-oxidase (tyrosinase). From 1955 he started working, in collaboration with Professor Antonio Caputo, on the properties of plasma proteins of the multiple myeloma and on the chemistry of lysozime. Voluntary Assistant at the Biochemistry Chair (University of Rome) from 1958 to 1966, he obtained the qualification for University teaching in Biochemistry in 1966. In 1968 he became Director of the Biochemistry Laboratory of the Regina Elena Institute, where he continued working throughout his entire career, until his retirement in 2002. He started his scientific career gaining international recognition for his outstanding achievements in investigations on several types of proteins, among which haemoglobins, tyrosinase, glycoproteins, peroxidases, muscle glycogen phosphorilase B, cartilage proteoglycan and cytochrome oxidase (nitrate reductase). On these subjects, he was author or co-author of several articles in international journals, especially in collaboration with scientists of the Rome University Biochemistry Chair, including Antonini, Brunori, Rossi-Fanelli, Wyman and Kertész. Worth of mention in that time were also his investigations on the immunological detection of haemoglobin in bones of ancient Roman times and iron and neolithic ages, a result of his great passion for archeology. From the early ‘70s onwards, Romano started focusing his scientific activity in the field of Environmental Carcinogenesis, a discipline of greatest interest to him, for which he will be best remembered. It was at that time that Romano started a long-lasting, voluntary and fruitful relationship for the rest of his career with researchers of the Istituto Superiore di Sanità (ISS), particularly Professor Angelo Carere and his collaborators, involved in the fields of Environmental Mutagenesis and Carcinogenesis. In these fields, among his best-known papers one can remember those on hair dyes, aromatic amines, polycyclic aromatic hydrocarbons, biomonitoring of occupational exposure to genotoxic carcinogens, DNA adducts, modulation of DNA binding by specific immunological response. In parallel to the experimental work, he greatly contributed to environmental carcinogenesis at a theoretical level by the development and evaluation of methods for assessment or prediction of risks associated to human exposure to environmental carcinogens. In this context, original papers were those relative to the prediction of rodent carcinogenicity by the US National Toxicology Program, (Q)SAR identification of mutagens and carcinogens, cancer risk assessment of direct acting carcinogens, low doses and thresholds in genotoxicity. Another important contribution was his decisive role for the realization in the ISS of a Data Base Bank on Carcinogens, available at www.iss.it/sitp/spps/bdsc. Finally, Romano has served the discipline of Environmental Carcinogenesis carrying out an excellent advising activity, playing a prominent role first in the Ministerial Committee on Mutagenesis, Carcinogenesis and Teratogenesis and later in the National Advisory Committee on Toxicology. His advising activity was always carried out with excellent competence, independence of judgement and great integrity. Romano was not only an eminent scientist, but also a man of great talent and vision, who was exceptionally endowed with gentleness and warmth. His intellectual sharpness and incredibly vast knowledge, together with great wisdom and pursuit of social justice characterized his lifetime achievements. He was never haughty as often happens in the science world. Nothing to him was given for granted or considered irrelevant. Very patient in explaining his ideas and convictions, he was always ready to “re-start from the beginning”. In addition to science, Romano showed great interest to other fields like archaeology (especially Roman and Aegyptian), history, architecture and music. He was a ANN IST SUPER SANITÀ 2006 | VOL. 42, NO. 2: 109-112 talented player of cello and interpreter of old classic pieces in a trio and an extraordinary guide for visits of churches, ruins, monuments in Rome and surrounds. A lot of persons, italians or foreigners, recall with great pleasure these guided visits with Romano in places like the Roman Forum and Palatine, Ostia Antica and Villa Adriana. Romano will be remembered not only as an eminent scientist, but also as a very friendly person, who was each time eager to share his vast learning with everyone who had the luck to know him. Angelo Carere Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy Selected publications of Professor Romano Zito 1. Benigni R, Zito R. The second National toxicology program comparative exercise on the prediction of rodent carcinogenicity: definitive results. Mutat Res 2004;566(1):49-63. 15. Chersi A, Houghten RA, Chillemi F, Zito R, Centis D. Specificity of rabbit antibodies elicited by related synthetic peptides. Z Naturforsch [C] 1986;41(5-6):613-7. 2. Benigni R, Zito R. Designing safer drugs: (Q)SAR-based identification of mutagens and carcinogens. Curr Top Med Chem 2003;3(11):1289-300. 16. Ascenzi A, Brunori M, Citro G, Zito R. Immunological detection of hemoglobin in bones of ancient Roman times and of Iron and Eneolithic Ages. Proc Natl Acad Sci USA 1985;82(21):7170-2. 3. Zito R. Low doses and thresholds in genotoxicity: from theories to experiments. J Exp Clin Cancer Res 2001;20(3):315-25. 17. Crebelli R, Aquilina G, Falcone E, Carere A, Caperle M, Crespi M, Zito R. Monitoring of urinary mutagenicity in workers exposed to low doses of 2,4,7-trinitro-9-fluorenone. Scand J Work Environ Health 1985;11(4):295-300. 4. Verdina A, Zito R, Federico A, Falasca G, Galati R. Divergent synergic effects in carcinogenesis initiation by simultaneous exposure to two genotoxic carcinogens. In Vivo 2000;14(6):753-6. 5. Zito R. Cancer risk assessment of direct acting carcinogens. J Exp Clin Cancer Res 1999;18(3):273-8. 6. Bucci F, Galati R, Zito R, Falasca G, Federico A, Verdina A. Identification of optimal conditions for the detection of benzo[a]pyrene-DNA adducts by enzyme-linked immunoadsorbent assays (ELISA). Anticancer Res 1998;18(4A):2669-74. 18. Silvestrini MC, Citro G, Colosimo A, Chersi A, Zito R, Brunori M. Purification of Pseudomonas cytochrome oxidase (or nitrite reductase) by immunological methods. Anal Biochem 1983;129(2): 318-25. 19. Albano G, Carere A, Crebelli R, Zito R. Mutagenicity of commercial hair dyes in Salmonella typhimurium TA98. Food Chem Toxicol 1982;20(2):171-5. 7. Galati R, Federico A, Cortese G, Zito R. Determination of serum levels of 2,6 diethylaniline in laboratory animal treated with Alachlor. Anticancer Res 1998;18(2A):979-82. 20. Citro G, Zito R, Marcante ML, Galdieri M, Floridi A, De Martino C. Sertoli cells of adult rats in vitro. III. Purification of androgen-binding protein from the culture medium. Experientia 1982 15;38(3):406-7. 8. Benigni R, Andreoli C, Zito R. Prediction of rodent carcinogenicity of further 30 chemicals bioassayed by the U.S. National Toxicology Program. Environ Health Perspect 1996;104S(5): 1041-4. 21. Crebelli R, Conti L, Carere A, Zito R. Mutagenicity of commercial p-phenylenediamine and of an oxidation mixture of p-phenylenediamine and resorcinol in Salmonella typhimurium TA98. Food Cosmet Toxicol 1981;19(1):79-84. 9. Benigni R, Andreoli C, Zito R. Prediction of rodent carcinogenicity of further 30 chemicals bioassayed by the U.S. National Toxicology Program. Environ Health Perspect 1996;104 Suppl 5:1041-4. 22. Silvestrini MC, Colosimo A, Brunori M, Citro G, Zito R. Some immunochemical properties of Pseudomonas aeruginosa cytochrome oxidase (or nitrate reductase). FEBS Lett 1980 21;113(1):85-9. 10. Verdina A, Zito R, Cortese G, Leopardi P, Marcon F, Zijno A, Crebelli R. Induction of humoral immunity toward 2acetylaminofluorene in mice: modulation of DNA binding after 4 weeks dietary exposure to the carcinogen. Carcinogenesis 1996;17(8):1705-9. 23. Prisco G, Zito R, Cacace MG. Nitration of functional tyrosyl residues in rabbit muscle phosphorylase B. Biochem Biophys Res Commun 1977;76(3):850-4. 11. Verdina A, Zito R, Cortese G, Zijno A, Crebelli R. Modulation of DNA binding in vivo by specific humoral immunological response: a novel host factor in environmental carcinogenesis? Environ Health Perspect 1996;104 Suppl 3:679-82. 12. Citro G, Galati R, Verdina A, Marini S, Zito R, Giardina B. Activation of 2,4-diaminotoluene to proximate carcinogens in vitro, and assay of DNA adducts. Xenobiotica 1993;23(3):31725. 24. Quintarelli G, Vocaturo A, Zito R, Roden L. The effects of acetylation on the binding region of cartilage proteoglycans to hyaluronic acid. Experientia 1977;33(3):298-9. 25. Chersi A, Zito R. Isolation of tryptophan-containing peptides by adsorption chromatography. Anal Biochem 1976;73(2):471-6. 26. Cacace MG, Di Prisco G, Zito R. Reversible modification of tyrosyl residues in rabbit muscle glycogen phosphorylase b by N-acetylimidazole. FEBS Lett 1976;62(3):338-41. 27. Quintarelli G, Bellocci M, Zito R. Structural features of insoluble elastin. Histochemie 1973;37(1):49-60. 13. Lendaro E, Ippoliti R, Bellelli A, Brunori M, Zito R, Citro G, Ascenzi A. Brief communication on the problem of immunological detection of antigens in skeletal remains. Am J Phys Anthropol 1991;86(3):429-32. 28. Cervone F, Diaz Brito J, Di Prisco G, Garofano F, Norona LG, Traniello S, Zito R. Simple procedures for the separation and identification of bovine milk whey proteins. Biochim Biophys Acta 1973;295(2):555-63. 14. Marini S, Citro G, Di Cesare S, Zito R, Giardina B. Production and characterization of monoclonal antibodies against DNA single ring diamines adducts. Hybridoma 1988;7(2):193-203. 29. Kertesz D, Rotilio G, Brunori M, Zito R, Antonini E. Kinetics of reconstitutioin of polyphenoloxidase from apoenzyme and copper. Biochem Biophys Res Commun 1972;49(5):1208-15. 111 112 ANN IST SUPER SANITÀ 2006 | VOL. 42, NO. 109-112 30. Kertesz D, Brunori M, Zito R, Antonini E. Transient kinetic studies of DOPA oxidation by polyphenoloxidase. Biochim Biophys Acta 1971;250(2):306-10. 31. Quintarelli G, Cifonelli JA, Zito R. On phosphotungstic acid staining. II. J Histochem Cytochem 1971;19(11):648-53. 32. Quintarelli G, Zito R, Cifonelli JA. On phosphotungstic acid staining. I. J Histochem Cytochem 1971;19(11):641-7. 33. Guerritore D, Zito R. The terminal groups of chlorocruorin. Biochim Biophys Acta 1971;229(3):720-3. 34. Zito R, Marcante ML, Floridi A, Caputo A. Tyrosyl residues and immunochemical properties of glycoproteins. Biochim Biophys Acta 1969;194(1):74-80. 35. Appella E, Zito R. A chemical study of lactate dehydrogenase isozyme B. Ann N Y Acad Sci 1968;151(1):568-77. 36. Brunori M, Amiconi G, Antonin E, Wyman J, Zito R, Fanelli AR. The transition between ‘acid’ and ‘alkaline’ ferric heme proteins. Biochim Biophys Acta 1968;154(2):315-22. 37. Tentori L, Vivaldi G, Carta S, Velani S, Zito R. The hemoglobin of amphibia. V. The amino-terminal residues and the carboxylterminal sequences of the hemoglobin of Rana esculenta L. Biochim Biophys Acta 1967;133(1):177-80. 38. Caputo A, Marcante ML, Zito R. The structure of alpha-1-glycoprotein isolated from Yoshida ascites tumour. Digestion with pronase and preparation of the glycopeptide. Br J Exp Pathol 1966;47(6):599-604. 39. Marino G, Scardi V, Zito R. Amino acid composition and terminal residues of aspartate aminotransferase from ox heart. Biochem J 1966;99(3):595-8. 40. Marino G, Greco AM, Scardi V, Zito R. Purification and general properties of aspartate aminotransferase of ox heart. Biochem J 1966;99(3):589-94. 41. Marino G, Scardi V, Zito R. [On the identity of 2 constituent monomers of bovine heart aspartate aminotransferases] Boll Soc Ital Biol Sper 1966 Feb 28;42(4):168-9. 42. Kertesz D, Antonini E, Brunori M, Wyman J, Zito R. Studies on the equilibria and kinetics of the reactions of peroxidases with ligands. I. The reaction of ferroperoxidases with carbon monoxide. Biochemistry 1965;4(12):2672-6. 43. Brunori M, Antonini E, Wyman J, Zito R, Taylor JF, RossiFanelli A. Studies on the oxidation-reduction potentials of heme proteins. II. Carboxypeptidase digest of human hemoglobin. J Biol Chem 1964;239:2340-4. 44. Marino G, Zito R, Scardi V. [Aspartate aminotransferase from bovine brain. II. Properties]. Boll Soc Ital Biol Sper 1964;40(12):720-1. 45. Zito R, Antonini E, Wyman J. The effect of oxygenation on the rate of digestion of human hemoglobins by carboxypeptidases. J Biol Chem 1964;239:1804-8. 46. Zito R, Marcante ML, Caputo A. The structure of the mucoprotein purified from yoshida ascites tumor. Acta Unio Int Contra Cancrum 1964;20:1146-8. 47. Cassingena R, Zito R, Miggiano V, Merucci P. Further comparative studies on two isogenic cell lines of autologous origin, one of which is tumor-producing. Oncology 1964;17:166-96. 48. Ferrini U, Zito R. Modification of histidine by ultraviolet irradiation of lysozyme. J Biol Chem 1963;238:3824-5. 49. Cassingena R, Zito R, Miggiano V, Merucci P. [Further comparative studies of 2 isogenic lines of cells of autologous origin, including 1 tumorigenic line]. Ann Ist Super Sanità 1963;26:727-51. 50. Kertesz D, Zito R. Kinetic studies of the polyphenoloxidase action; kinetics in the presence of reducing agents. Biochim Biophys Acta 1962;64:153-67. 51. Kertesz D, Zito R. The indirect oxidation of reduced cytochrome c by polyphenol oxidase. Biochim Biophys Acta 1962;59:752-4. 52. Antonini E, Wyman J, Zito R, Rossi-Fanelli A, Caputo A. Studies on carboxypeptidase digests of human hemoglobin. J Biol Chem 1961;236:PC60-3. 53. Ferrini U, Zito R. Action of trypsin on Bence-Jones protein derivatives. Nature 1961;189:485. 54. Kertesz D, Zito R. Polyphenoloxidase (tyrosinase): purification and molecular properties. Nature 1957;179(4568):1017-8. 55. Kertesz D, Zito R. Polyphénoloxidase (tyrosine): purification propriétés moléculaires. C R Seances Soc Biol Fil 1957;151(6):1078-81. 56. Caputo A, Zito R. Les groupes N et C terminaux de la séralbumine humaine normale et de la sérumalbumine de myélome. Bull Soc Chim Biol (Paris) 1955;37(12):1255-61. 57. Teti M, Zito R. [Histochemistry of necrotic tissue in Ehrlich adenocarcinoma]. Riv Ist Sieroter Ital 1954;29(5):395-402.
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