Preferential induction of AT-TA transversion, but not deletions, by chlorambucil at the hisG428 site of Salmonella typhimurium TA102.
The chemotherapeutic agent chlorambucil effectively induces deletion mutations in mouse germ cells. The possibility that this chemical also effectively induces deletion mutations in bacterial DNA was examined using Ames Salmonella tester strains. Chlorambucil was mutagenic only to strains TA102 (hisG428, rfa/pKM101) and YG2975 (hisG46, rfa/pKM101) when S9 mix was absent. Since strain TA102 can detect short deletions, the mutational changes of TA102 induced by this agent without S9 mix were directly determined by the DNA sequencing technique. It turned out that chlorambucil did not induce deletion mutations but preferentially induced AT-TA transversions at the hisG428 site of plasmid pAQ1 of strain TA102. These results caution that the positive results induced by chlorambucil in mutagenicity tests do not necessarily mean the occurrence of deletions.
Yamada
M
M
Division of Genetics and Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.
Sofuni
T
T
Nohmi
T
T
D000818:Animals; D001483:Base Sequence; D001711:Biotransformation; D002699:Chlorambucil / Q000494:pharmacology*; D002872:Chromosome Deletion; D005798:Genes, Bacterial / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D009153:Mutagens; D009838:Oligodeoxyribonucleotides; D002699:Chlorambucil