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.
Nesnow
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Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Garland
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H
Curtis
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G
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage; D002273:Carcinogens / Q000008:administration & dosage*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D008748:Methylcholanthrene / Q000008:administration & dosage; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene