Role of DNA Repair in Physical, Chemical and Viral Carcinogenesis
It is generally assumed that a great variety of carcinogen-induced changes to DNA lead to one type of DNA repair synthesis which can be detected by an unscheduled uptake of labelled DNA precursors. Thus, by measuring DNA repair synthesis data can be obtained about DNA damages without defining the type of carcinogen-DNA bondage and the type of alterations. There is evidence to suggest that the removal of carcinogen-induced products occurs at various rates after the initial damage. Even if extensive dose-response relationships have been worked only in few cases, it can be assumed that the rate of excision is dose-dependent and follows a general kinetics. In the case of UV-irradiation, according to the sensibility of the various cell lines, the rate of excision in vitro is dependent on the dose of irradiation and gradually drops toward a plateau reached, even at the highest doses, within 24 hours. Similarly, when cultured human fibroblasts are exposed to one low dose of 4N00, the study of the kinetics of unscheduled incorporation of thymidine indicates that the repair has occurred in the first few hours after the treatment. If a second dose of carcinogen is given the cells do not respond at a normal level, yet when repair of the first dose is completed further DNA damages are effectively repaired.
KeywordsSarcoma Thymidine Guanine Nitroso Methylcholanthrene
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