Genetic properties for the suppression of development of putative preneoplastic glutathione S-transferase placental form-positive foci in the liver of carcinogen-resistant DRH strain rats

The post-initiation stage of hepatocarcinogenesis was investigated in carci nogen-resistant inbred DRH rats and the parental strain, carcinogen-sensiti ve Donryu rats. Male rats at 5 weeks of age from both strains were treated with N-nitrosodiethylamine (200 mg/kg i.p.) followed by feeding with a diet containing 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from 2 weeks la ter and were then subjected to partial hepatectomy at 1 week later. At 8 we eks after the start of treatment, the mean area occupied by glutathione S-t ransferase placental form (GST-P)-positive lesions was about 30% in Donryu rats but less than 4% in DRH rats despite the presence of comparable number s of foci in the livers of both strains. These observations suggested that clonal expansion of GST-P-positive foci in DRH rat liver was significantly suppressed under these conditions. Furthermore, this genetic property was d ominantly inherited in the Fl rats by crosses of DRH and carcinogen-sensiti ve inbred F344 rats; that is, the induction of GST-P mRNA in the livers of F344 x DRH El rats was dominantly suppressed after administration of 3'-Me- DAB for 8 weeks as compared with parental F344 rats under the same conditio ns. We compared the intrinsic properties related to growth potential of liv er cells between adult DRH and Donryu rats. DRH rat liver showed retarded a nd/or reduced DNA synthesis after partial hepatectomy or a single i.v, inje ction of lead nitrate and lower activity of telomerase induced by 3'-Me-DAB administration for 1 week, as compared with the Donryu rat liver. The intr insic properties observed in this study may be related, at least in part, t o the low incidence of liver tumors induced by hepatocarcinogens in DRH rat s. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.