Genotoxicity of 2-amino-6-N-hydroxyadenine (AHA) to mouse lymphoma and CHO cells.
2-Amino-6-N-hydroxyadenine (AHA) treated L5178Y/TK (+/-)-3.7.2C mouse lymphoma cells were evaluated for mutations at the tk, hgprt, and Na+/K+ ATPase loci, as well as for gross chromosome aberrations and induction of micronuclei. In addition, AHA was evaluated for its ability to induce HGPRT mutants in CHO cells. AHA was found to induce mutations at all evaluated loci and in both cell types. The TK mutants were primarily large colonies although a few small colonies were also induced, particularly at the higher concentrations. Preliminary cytogenetic analysis of AHA-treated mouse lymphoma cells indicated that some gross aberrations but not micronuclei were induced. The 20 small-colony TK mutants evaluated by banded karyotype indicate that only a small fraction (2 of 20) showed chromosome 11 abnormalities. From these studies, it appears that AHA may be one of a very few chemicals that is capable of inducing multi-locus point mutations, with only slight clastogenic activity. Particularly at the higher concentrations, some of the mutants may contain multi-locus point mutations that result in slow growth.
Moore
M M
MM
Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NY 27711.
Harrington-Brock
K
K
Parker
L
L
Doerr
C L
CL
Hozier
J C
JC
D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D051379:Mice; D015162:Micronucleus Tests; D016296:Mutagenesis; D009153:Mutagens; D010042:Ouabain / Q000633:toxicity; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013866:Thioguanine / Q000633:toxicity; D014407:Tumor Cells, Cultured
D009153:Mutagens; D010042:Ouabain; C030632:2-amino-N(6)-hydroxyadenine; D000254:Sodium-Potassium-Exchanging ATPase; D013866:Thioguanine; D000225:Adenine