Genetic background of high incidence of spontaneous tumors in BDX rats.

Genetic background of high incidence of spontaneous tumors in BDX rats was investigated with respect to susceptibility to physical or chemical agents and immune response. Percentages of colony forming ability of normal embryo fibroblasts from BDX rats after exposure to various doses of ultraviolet (UV) light, X-rays and Mitomycin C were almost identical to those of cells from control F344 rats. Furthermore, BDX rats showed similar level of rosette forming cells, blastogenic response, and plaque forming cell (PFC) response as compared with WKA rats used as a control, although BDX rats showed higher natural killer (NK) cell activity. These results indicate that high incidence of spontaneous tumors in BDX rats is not due to some defects in DNA repair or immune response. In 3 methylcholanthrene (MCA) carcinogenesis, however, BDX rats developed tumors very early; the mean latency periods for development of MCA-induced tumors were 135 days in BDX rats and 256 days in F344 rats. Measurement of the inducibility of specific aryl hydrocarbon hydroxylase (AHH) activity in liver microsomes revealed that BDX rats showed higher inducibility than F344 rats: the inducibilities were 23.7 in BDX rats and 5.7 in F344 rats. Higher inducibility of AHH in BDX rats seemed to be parallel to earlier development of tumors in MCA-carcinogenesis in the rats. Thus, it is most likely that high incidence of spontaneous tumors in BDX rats is due to high susceptibility to some chemical carcinogens which may be contained in foods or drinking water in a small dose.