Biological significance of aminophenyl-β-carboline derivatives formed from co-mutagenic action of β-carbolines and aniline and o-toluidine and its effect on tumorigenesis in humans: A review

Publication date: Available online 28 January 2020Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Yukari Totsuka, Keiji WakabayashiAbstractNorharman exists in cigarette smoke and cooked foods and is non-mutagenic among Salmonella strains but mutagenic to S. typhimurium TA98 and YG1024 in the presence of S9 mix and aniline and o-toluidine. Co-mutagenesis of β-carbolines and aniline and o-toluidine occurs through the formation of novel mutagenic aminophenyl-β-carboline derivatives including 9-(4’-aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman] (APNH)] and 9-(4’- amino-3’-methylphenyl)-9H-pyrido[3,4-b]indole [aminomethylphenylnorharman] (AMPNH)]. Since humans are often simultaneously exposed to β-carbolines and aniline and o-toluidine, their effects on humans should be clarified. The most potent of these, APNH, induced both point mutations and small deletions in the liver and colon of gpt delta transgenic mice. Major APNH-induced mutations in the liver occurred at a G:C base pair, suggesting that APNH-DNA adducts (dG-C8-APNH) are potentially involved in these mutations. Furthermore, APNH induced hepatic and colon tumors harboring K-ras, β-catenin, and Apc mutations in F344 rats, with high incidence. Mutations at G:C base pairs were predominant, similar to those in the in vivo mutation assay using gpt delta mice. Moreover, APNH detected in human urine samples obtained from both healthy volunteers on a normal diet and inpat...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research