Inhibition of morphological transformation of C3H10T1/2CL8 mouse embryo cells by multiple carcinogen treatments.

C3H10T1/2CL8 cells treated on the first day after seeding with benzo[a]pyrene (B[a]P) and then treated again with B[a]P displayed an inhibited response of morphological transformation if the second treatment was administered from 14 days to 33 days after seeding. Under these conditions the cells exhibited up to 100% inhibition of morphological transformation, the extent of inhibition being related to the concentration of B[a]P administered in the second treatment. 3-Methylcholanthrene (3MC) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) also inhibited B[a]P-induced morphological transformation as a function of concentration when administered to cells 21 days after the initial B[a]P treatment. Delayed recovery of transformed foci was examined in cells treated with B[a]P on days 1 and 22 and scored 6-9 weeks after the first B[a]P treatment. No recovery of cell transformants was observed. Reconstruction experiments with normal and transformed C3H10T1/2CL8 cells suggested that selective cytotoxicity to incipient transformed cells could account for the inhibition by MNNG, but could not account for up to 50% of the inhibition induced by the second treatment of B[a]P or 3MC.