Dose-response studies on neoplastic transformation of BALB/3T3 clone A31-1-1 cells by aflatoxin B1, benzidine, benzo[a]pyrene, 3-methylcholanthrene, and N-methyl-N'-nitro-N-nitrosoguanidine.
The BALB/3T3 clone A31-1-1 mouse embryo cell line at passages 7 to 13 was selected for morphologic studies of neoplastic transformation by carcinogens of different chemical classes, in the absence of any added extracellular metabolic activation. Dose-related transforming activity was demonstrated for the carcinogens aflatoxin B1 (AFB) and benzidine (BZ) not previously reported in this system, and was confirmed for benzo[a]pyrene (BP), 3-methylcholanthrene (MCA), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Spontaneous transformation per cells at risk was low (0.14 type III foci x 10(-4), while chemically induced transformation was 2 to 3 orders of magnitude higher with all compounds. The molar concentration of carcinogens in complete medium, required to induce a transformation frequency of 1.0 type III foci x 10(-3) showed the highest level of activity for BP (0.04 microns), an intermediate level for AFB (0.2 to 1.4 microns), MCA (1.1 micron), and MNNG (2.3 microns), and the lowest level of activity for BZ (30.0 microns). The dose-related induction of morphological transformation in this clone by carcinogens of different classes indicates the potential value of this biological system in quantitative studies of carcinogen combinations, especially at low dose levels.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D001560:Benzidines / Q000494:pharmacology; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D002999:Clone Cells; D008748:Methylcholanthrene / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C
D000348:Aflatoxins; D001560:Benzidines; D001580:Benzopyrenes; D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; C029876:benzidine; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D016604:Aflatoxin B1