Mutations Induced by 1-Nitrosopyrene and Related Compounds during DNA Replicationin Human Cells and Induction of Homologous Recombination by These Compounds

摘要

The study was designed to investigate the mechanisms by which certaincarcinogenic compounds found in diesel exhaust particles and structurally-related N-substituted aryl carcinogens induce base substitution mutations and homologous recombination events in mammalian cells in culture. All four N-substituted aryl compounds produced mainly base substitutions involving guanosine-cytosine (G-C) base pairs, primarily G-C --> thymidine-adenine transversions. However 1,6-dinitropyrene adducts also induced a significant proportion of single G-C base-pair deletions. Each agent induced its own unique set of mutational hot spots. There was a good correlation between hot spots for initial adduct formation and for subsequent mutation induction. The frequency of recombination induced by 1-nitrosopyrene was compared in the three human cell strains, which differed in their excision repair capacities. The data strongly suggest that the presence of unexcised DNA adducts, rather than the excision repair process itself, stimulates intrachromosomal homologous recombination in human cells.