Relationship between in vivo mitomycin C exposure, sister chromatid exchange induction and in vitro mitogenic proliferation. II. Effect of aging on spleen cell mitogenesis and sister chromatid exchange induction.

In vivo administration of mitomycin C (MMC) produces an increase in both the frequencies of sister chromatid exchange (SCE) as well as inhibition of in vitro mitogenic responses. At low concentrations of MMC (2 mg/kg) spleen cell suspensions from both young and old mice showed similar patterns of mitogen inhibition and increased SCE frequencies. At high MMC concentrations (5 mg/kg) significant differences between young and old responses were observed. Spleen cells from young animals displayed mitogen-inhibition curves which plateaued with increasing doses of MMC, while the cells from old animals displayed a continuing increase in mitogenic inhibition. MMC-induced SCE frequencies revealed a complementary pattern: increasing SCE frequencies as a function of MMC concentration in young spleen cells while SCE levels plateaued in old spleen cell populations. The results of these studies suggest (1) that an inverse relationship exists between sister chromatid exchange induction and mitogenic response, (2) that cells from older animals may have an increased sensitivity to high levels of DNA damage (5 mg/kg MMC), and (3) that this sensitivity may be expressed functionally by increased inhibition of in vitro mitogenic responses.