In contrast, the apurinic site-containing genome gave rise only to targeted mutations. While most mutations were targeted to the site of the lesion, a significant fraction (13%) occurred at the base 5′ to the modified guanine. It is concluded that the AFB1-N7-Gua adduct, and not the apurinic site, has genetic requirements for mutagenesis that best explain mutations in aflatoxin-treated cells.
The G → T mutations of AFB1-N7-Gua, unlike those of the AFB1-N7-Gua-derived apurinic site, were much more strongly dependent on MucAB than UmuDC, a pattern matching that in intact cells treated with the toxin. The predominant mutation was G → T, identical to the principal mutation in human liver tumors believed to be induced by aflatoxin. Replication in SOS-induced Escherichia coli yielded a mutation frequency for AFB1-N7-Gua of 4%. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7- Gua) adduct was inserted into the single-stranded genome of bacteriophage M13.
The mutagenic activity of the major DNA adduct formed by the liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo.
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