STAMPA ANN_06_01 Pref. SEZ. I - Istituto Superiore di Sanità

ANN IST SUPER SANITÀ 2006 | VOL. 42, NO. 2: 109-112
“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
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
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 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
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
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):
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):
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
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
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
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.
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
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
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
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.