Association of carcinogen-resistant mechanisms of the inbred rat strain DRH with apoptosis

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A carcinogen-resistant inbred strain DRH rat developed from a closed colony of Domyu rats shows a remarkably low incidence of liver tumors during hepatocarcinogenesis by 3'-Me-DAB compared with Donryu rats.. Previously, we observed that DRH rats had also showed some resistance against tumorigenesis by 4NQO in the tongue. Recently, some genes have been reported which may be responsible for the resistance against hepatocarcinogenesis in DRH rats. However, there have been few reports on carcinogenesis in organs of DRH rats other than the liver. Furthermore, the mechanisms of resistance against hepatocarcinogenesis in DRH rats are not known.Suppression of apoptosis may be a factor required for carcinogenesis. The purpose of the present study is to investigate the participation of apoptosis in resistance against carcinogenesis in DRH rats. We first examined mRNA levels of bcl-2 and bax during carcinogenesis in the rat tongue. Although DRH rats showed some resistance in the early stage of carcinogenesis in the tongue by 4NQ0, we could detect no difference in the levels of bcl-2 and bax mRNA between DRH and Dontyu rats.To further study the effectiveness of mechanisms of apoptosis in DRH rats, lymphocytes were prepared and apoptosis was induced in vitro by Dexamethasone or Actinomycin D. Then, DNA fragmentation and expression of bcl-2 and bax mRNAs were estimated. We detected some differences in those estimations between DRH and Doniyu rats.The present results suggest that there exists some difference in the mechanisms of apoptosis in the two rat strains, which may be responsible for the resistance of DRH rats against carcinogenesis