Inversion of genetic predisposition to carcinogenesis in liver of two lines of mice selected for resistance (Car-R) or susceptibility (Car-S) to skincarcinogenesis

Two lines of mice, one resistant (Car-R) and one susceptible (Car-S) to ski n carcinogenesis, were produced by bi-directional selective breeding. To se e whether the characteristics of susceptibility or resistance to tumorigene sis were also expressed in the liver and lung, the two lines were submitted comparatively to treatment with 5,9-dimethyl dibenzo[c,g]carbazole (DiMeDB C), a potent hepatocarcinogenic derivative of the ubiquitous heterocyclic c arcinogenic pollutant, 7H-dibenzo[c,g]-carbazole (DBC). An inversion of gen etic predisposition to carcinogenesis in liver was observed. Car-R animals displayed rapid tumorigenesis in 100% of cases while Car-S mice were remark ably less sensitive, showing a 4-fold lower mean tumor multiplicity and a 4 -month longer latency time. In parallel adduct formation by DiMeDBC and DEC in liver DNA was analyzed by the P-32-postlabeling method, showing a remar kably higher level in Car-R mice than in Car-S animals. These data indicate that tissue-specific sensibility in carcinogenesis may involve gene expres sion at various levels. (C) 1998 Elsevier Science Ireland Ltd. All rights r eserved.