Methylated purines formed in DNA by dimethylnitrosamine in rats previously exposed to hepatotoxic and hepatocarcinogenic regimes: effects on the repair of O6-methylguanine.
Authors
Cooper, Donald PStyles, J
Bradbrook, C
Charlesworth, J
Chu, Y H
O'Connor, Peter J
Margison, Geoffrey P
Issue Date
1985-05
Metadata
Show full item recordAbstract
Studies of mammalian systems for the repair of O6-methylguanine in DNA have revealed large differences in the capacities of tissues and cells to perform this function and in the case of rat liver it has been shown that the O6-methylguanine repair system can be stimulated by exposure to hepatotoxic and hepatocarcinogenic regimes. In this report an assessment is made of possible relationships between toxic liver injury, DNA synthesis, cell proliferation and DNA repair by treating Wistar rats with agents selected to provide differing degrees of liver involvement. The effects of long-term (20 week) treatments with acetylaminofluorene (15 mg/kg/day), quinoxaline 1,4-dioxide (10 mg/kg/day), 4-aminobiphenyl-HCl (15 mg/kg/day) and pronethalol (20 mg/kg/day) were assessed, using the same strain of animals in which the original toxicity and carcinogenicity data were obtained. Repair of O6-methylguanine produced in liver DNA by a low, non-toxic dose (2 mg/kg) of [14C]dimethylnitrosamine was increased 3-4-fold throughout the period of treatment with acetylaminofluorene, to a lesser extent by quinoxaline 1,4-dioxide and 4-aminophenyl-HCl and not at all in the case of pronethalol. No evidence was obtained to indicate a direct relationship between O6-methylguanine repair and either the induced hepatotoxicity or the ensuing increased rates of DNA synthesis which occur following exposure to these agents.Citation
Methylated purines formed in DNA by dimethylnitrosamine in rats previously exposed to hepatotoxic and hepatocarcinogenic regimes: effects on the repair of O6-methylguanine. 1985, 53 (3):283-301 Chem Biol InteractJournal
Chemico-Biological InteractionsDOI
10.1016/S0009-2797(85)80105-8PubMed ID
2860979Type
ArticleLanguage
enISSN
0009-2797ae974a485f413a2113503eed53cd6c53
10.1016/S0009-2797(85)80105-8