Aflatoxin B1, 2-aminoanthracene, and 7,12-dimethylbenz[a]anthracene-induced frameshift mutations in human APRT.
Aflatoxin B1, 2-aminoanthracene, and 7,12-dimethylbenz[a]anthracene have been implicated in the etiology of human cancers. In this study, we demonstrate that these three chemicals can be activated by rat liver homogenate S9 coupled with NADPH coenzymes to produce a dose-dependent increase in the frequency of APRT reversion in the APRT-deficient human cell line HTD114. HTD114 contains single nucleotide insertions at different positions in each APRT allele and the spontaneous reversion frequency is < 10(-8). However, the highest reversion frequency induced by these chemicals is 1.2-2.0 x 10(-5), at least a 10(3)-fold increase over the frequency of spontaneous reversion. Reversion of either mutant allele was observed to be a consequence of a frame-restoring loss of a single nucleotide, which indicates that these three chemicals can function as frameshift mutagens in human cells.
Zhu
Y
Y
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
Bye
S
S
Stambrook
P J
PJ
Tischfield
J A
JA
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D016604:Aflatoxin B1 / Q000633:toxicity*; D000595:Amino Acid Sequence; D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D001483:Base Sequence; D001711:Biotransformation; D002460:Cell Line; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion
D000873:Anthracenes; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene; C006593:2-anthramine; D016604:Aflatoxin B1; D000228:Adenine Phosphoribosyltransferase