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Quantitative Aspects of Risk Assessment in Chemical Carcinogenesis - Symposium held in Rome/Italy, April 3-6, 1979 (Paperback, Softcover reprint of the original 1st ed. 1980)
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Quantitative Aspects of Risk Assessment in Chemical Carcinogenesis - Symposium held in Rome/Italy, April 3-6, 1979 (Paperback, Softcover reprint of the original 1st ed. 1980)
Series: Archives of Toxicology, 3
Expected to ship within 10 - 15 working days
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N-nitroso-compounds form an important class of carcinogenic
chemicals which may be of environmental importance (Druckrey et al.
, 1967; Magee et al. , 1976; IARC, 1978). The mechanism by which
these carcinogens initiate neoplastic growth is not well understood
but there is substantial evidence favoring the hypothesis that the
simple dialkylnitrosamines and alkylnitrosamides act by means of
their conversion to al- kylating agents. Alkylating species are
generated from the nitrosamines by metabolic activation and from
the nitrosamides by chemical decomposition at physiological pH. It
is widely believed that DNA is the critical alkylation target.
Alkylation takes place at at least 12 sites within the DNA molecule
(Lawley, 1976; Singer, 1976; Pegg, 1977a). Al- though alkylation at
the 7-position of guanine is the most extensive reaction with the
DNA bases and provides a reliable measurement of the degree of
interaction with the carcinogen (Swann and Magee, 1968, 1971),
recent experiments have suggested that alkylation of oxygen atoms
may be the critical reaction (Goth and Rajewsky, 1974; Margison and
Kleihues, 1975; Nicoll et aI. , 1975; Pegg, 1977a). These
laboratories have observed a correlation between the production and
persistence of 06-alkyl- guanine and the occurrence oftumors in a
variety of organs of rodents exposed to N-ni- troso-carcinogens. It
has, therefore, been suggested that the ability of tissues to
catalyze the removal of 06-alkylguanine from DNA may provide a
protective mechanism against carcinogenesis.
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