Induction of mutagenesis and transformation in BALB/c-3T3 clone A31-1 cells by diverse chemical carcinogens.
BALB/c-3T3 cells were employed to examine the genotoxic potential of a variety of known chemical carcinogens. BALB/c-3T3 cells displayed a dose-dependent transformation response to a variety of carcinogens (polycyclic hydrocarbons, methylating agents, ethylating agents, aflatoxin B1 [AFB1], and 4-nitroquinoline-N-oxide [4-NQO]). When the ability of these compounds to induce mutagenesis to resistance to the cardiac glycoside ouabain (OUAR) was examined, we found the short chain alkylating agents to be particularly effective mutagens, causing biologic effects at doses below those necessary to induce a transformation response. In contrast, the polycyclic hydrocarbons which were potent transforming agents were weaker, albeit significant, mutagens for the OUAR locus in this system, while AFB1 was quite weak. Further studies were performed with 5-azacytidine (5-AZA) and the nongenotoxic carcinogen cinnamyl anthranilate (ClN). 5-AZA was a potent transforming agent, but failed to cause mutagenesis. ClN similarly caused in vitro transformation. When a series of eight structurally diverse compounds were examined in both the BALB/c-3T3 and C3H10T1/2 mouse fibroblast transformation systems, the BALB/c-3T3 system was shown to be sensitive to a wide variety of potential carcinogens, whereas the C3H10T1/2 system proved routinely sensitive only to the polycyclic hydrocarbons.
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701.
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Lubet
R E
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Kouri
R A
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Curren
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Putman
L M
LM
Schechtman
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002273:Carcinogens; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation; D011083:Polycyclic Compounds / Q000494:pharmacology
D000477:Alkylating Agents; D002273:Carcinogens; D011083:Polycyclic Compounds; D001374:Azacitidine