Mechanism of activation of proximate mutagens in Ames' tester strains: the acetyl-CoA dependent enzyme in Salmonella typhimurium TA98 deficient in TA98/1,8-DNP6 catalyzes DNA-binding as the cause of mutagenicity.

The mechanism of activation of proximate mutagens in Ames' tester strains was described. 2-Hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) and 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were activated to DNA-binding species in the presence of acetyl-CoA by the enzyme(s) in Salmonella typhimurium TA98, and this enzyme was deficient in TA98/1,8-DNP6. Mutagenicity of N-OH-Glu-P-1 to TA98/1,8-DNP6 was much lower than that to TA98. Therefore, it was demonstrated that the acetyl-CoA dependent enzyme(s) activated N-OH-Glu-P-1 to the active form which could covalently bind to DNA and subsequently caused mutagenicity.