Mutagenic properties of N‐acetyl‐2‐aminofluorene and its metabolites in relation to the molecular mechanisms of carcinogenesis

Abstract

The genetic properties of the carcinogen N-acetyl-2-aminofluorene were compared with those of representatives of its suspected metabolites: the N-hydroxylamine, its acetic and sulphuric acid oxy-esters, as well as the I -and 3-hydroxylamines

Benzo[a]pyrene and Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced locomotor and reproductive senescence and altered biochemical parameters of oxidative damage in Canton-S Drosophila melanogaster

“…Successful toxicity testing of B[a]P in Drosophila melanogaster have however depended on genetically modified strains and most of these studies are mainly for mutagenicity and genotoxicity testing. Lee et al successfully used a repair-deficient strain for B[a]P-induced mutagenicity study [ 14 ], Fahmy and Fahmy used the 3-methyl and 6-hydroxymethyl derivatives of B[a]P in the Oregon-K strain [ 15 ], Frölich and Würgler created a tester strain by introducing chromosomes 1 and 2 from a wild-type strain with high CYP450-dependent metabolism linked to a gene on chromosome 2 for genotoxicity testing [ 16 ], Fujikawa et al also achieved genotoxicity testing of B[a]P using D. melanogaster stock comprising of meiotic recombination deficient double mutant males and females [ 17 ]. These studies are based on either the sex-linked recessive lethal test for mutagenesis, DNA repair assay or the somatic mutation and recombination tests (SMART) for genotoxicity testing.…”

The role of cytogenetic tests in detection and prevention of cancer

“…Studies that were undertaken some time ago established correlations between the chromosomal damage produced by carcinogenic chemicals and the molecular aberrations they may be involved in the induction of the carcinogenic process. In a study of the mutagenic properties of acetyl-2-aminofluorene and its metabolites in Drosophila, in relation to the molecular mechanisms of carcinogenesis [17,18], a subtle correlation between mutagenic selectiveness and the carcinogenic potential of this series of compounds was demonstrated. The carcinogenic parent amine, its N-hydroxylamines, and the acetoxy derivative were all initially specific for the bobbed (bb) loci; this is in accord with the concept that the rRNA genes might be significant in the initiation of cancer.…”