Mutation spectrum of cigarette smoke condensate in Salmonella: comparison to mutations in smoking-associated tumors

TA transversions and approximately 20% GC-->AT transitions at the base-substitution allele (hisG46) in strain TA100. This spectrum was similar to those of the polycyclic aromatic hydrocarbon (PAH) benzo[alpha]pyrene and various aromatic amines such as 4-aminobiphenyl and Glu-P-1, all of which are present in CSC. This spectrum was also similar to that produced by PAHs in other bacteria, mammalian cells, and rodents as well as to that of the p53 gene in lung tumors from smokers. The results in Salmonella are consistent with a role for the PAH component of cigarette smoke in the base-substitution specificity found in the p53 gene of smoking-associated lung tumors. At the frameshift allele in strains TA1538 and TA98, CSC induced only a hotspot 2-base deletion, which is a mutation spectrum that is identical to that induced by the heterocyclic amine pyrolysate products of amino acids, such as Glu-P-1. This is consistent with bioassay-directed fractionation studies showing that aromatic amines account for most of the frameshift specificity of CSC in Salmonella. Rodent and human studies indicate that aromatic amines are responsible for smoking-associated bladder cancer. Repeated freezing and thawing of the CSC samples changed the chemical composition of the mixtures as evidenced by the production of an altered mutation spectrum. This emphasizes the necessity of proper storage and handling of labile complex mixtures. This study (i) confirms our previous studies showing that the mutation spectrum of a complex mixture reflects the dominance of one or a few classes of chemical mutagens within the mixture, and (ii) illustrates the potential of bioassay-directed molecular analysis for identifying the chemical classes in a complex mixture that are responsible for specific classes of mutation and tumor types produced by the mixture. -->

ISSN:	1460-2180 0143-3334
DOI:	10.1093/carcin/16.10.2535
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a135c7c7c4441768d67b8cef54b2f2c3 https://doi.org/10.1093/carcin/16.10.2535
Přírůstkové číslo:	edsair.doi.dedup.....a135c7c7c4441768d67b8cef54b2f2c3
Autor:	David M. DeMarini, Melissa L. Shelton, Jessie G. Levine
Rok vydání:	1995
Předmět:	DNA Bacterial Salmonella typhimurium Cancer Research Salmonella Molecular Sequence Data Polycyclic aromatic hydrocarbon Mutagen medicine.disease_cause Frameshift mutation chemistry.chemical_compound Species Specificity Smoke Benzo(a)pyrene medicine Animals Humans Alleles Biotransformation Sequence Deletion chemistry.chemical_classification Base Sequence Mutagenicity Tests Hybridization probe Smoking Nucleic acid sequence DNA Neoplasm General Medicine Urinary Bladder Neoplasms chemistry Biochemistry Mutagenesis Heterocyclic amine Microsomes Liver Pyrene Mutagens
Zdroj:	Carcinogenesis. 16:2535-2542
ISSN:	1460-2180 0143-3334
DOI:	10.1093/carcin/16.10.2535
Popis:	We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 1600 revertants of Salmonella induced by cigarette smoke condensate (CSC) in the presence of S9. CSC induced approximately 80% GC-->TA transversions and approximately 20% GC-->AT transitions at the base-substitution allele (hisG46) in strain TA100. This spectrum was similar to those of the polycyclic aromatic hydrocarbon (PAH) benzo[alpha]pyrene and various aromatic amines such as 4-aminobiphenyl and Glu-P-1, all of which are present in CSC. This spectrum was also similar to that produced by PAHs in other bacteria, mammalian cells, and rodents as well as to that of the p53 gene in lung tumors from smokers. The results in Salmonella are consistent with a role for the PAH component of cigarette smoke in the base-substitution specificity found in the p53 gene of smoking-associated lung tumors. At the frameshift allele in strains TA1538 and TA98, CSC induced only a hotspot 2-base deletion, which is a mutation spectrum that is identical to that induced by the heterocyclic amine pyrolysate products of amino acids, such as Glu-P-1. This is consistent with bioassay-directed fractionation studies showing that aromatic amines account for most of the frameshift specificity of CSC in Salmonella. Rodent and human studies indicate that aromatic amines are responsible for smoking-associated bladder cancer. Repeated freezing and thawing of the CSC samples changed the chemical composition of the mixtures as evidenced by the production of an altered mutation spectrum. This emphasizes the necessity of proper storage and handling of labile complex mixtures. This study (i) confirms our previous studies showing that the mutation spectrum of a complex mixture reflects the dominance of one or a few classes of chemical mutagens within the mixture, and (ii) illustrates the potential of bioassay-directed molecular analysis for identifying the chemical classes in a complex mixture that are responsible for specific classes of mutation and tumor types produced by the mixture.
Databáze:	OpenAIRE
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