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Induction of mutagenesis and transformation in BALB/c‐3T3 clone A31‐1 cells by diverse chemical carcinogens
Author(s) -
Lubet Ronald A.,
Kouri Richard E.,
Curren Roger A.,
Putman Donald L.,
Schechtman Leonard M.,
McCormack J. R.
Publication year - 1990
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850160103
Subject(s) - mutagenesis , clone (java method) , carcinogen , transformation (genetics) , biology , genetics , mutation , microbiology and biotechnology , chemistry , dna , gene
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 B 1 [AFB 1 ], and 4‐nitroquinoline‐N‐oxide [4‐NQO]). When the ability of these compounds to induce mutagenesis to resistance to the cardiac glycoside ouabain (OUA R ) 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 OUA R locus in this system, while AFB 1 was quite weak. Further studies were performed with 5‐azacytidine (5‐AZA) and the nongenotoxic carcinogen cinnamyl anthranilate (CIN). 5‐AZA was a potent transforming agent, but failed to cause mutagenesis. CIN 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.