Effects of Salmonella assay negative and positive carcinogens on intrachromosomal recombination in G1-arrested yeast cells. 1996

A Galli, and R H Schiestl
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.

A wide variety of carcinogens including Ames assay (Salmonella) positive as well as Salmonella-negative carcinogens induce intrachromosomal recombination (DEL recombination) in strain RS112 of Saccharomyces cerevisiae. It has been previously shown that the Salmonella-positive carcinogens ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4-NQO) and the Salmonella-negative carcinogens safrole, benzene, thiourea, carbon tetrachloride and urethane induce DEL recombination in G2-arrested yeast cells. DEL recombination is preferentially induced by safrole, benzene and carbon tetrachloride in G2-arrested cells which might be explained by preferential induction of unequal sister chromatid recombination leading to deletions. To test this, cells of strain RS112 were arrested in the G1 phase of the cell cycle, exposed to these carcinogens and the frequencies of DEL and interchromosomal recombination (ICR) were determined. EMS, MMS and 4-NQO induced DEL recombination and ICR in G1-arrested cells with a linear dose-response curve. In contrast, the Salmonella-negative carcinogens safrole, benzene, carbon tetrachloride, thiourea and urethane induced DEL recombination and ICR with a threshold below which no significant increase was seen and only at already cytotoxic doses. EMS, MMS and 4-NQO were more recombinagenic in previous experiments with growing cells than in G1-arrested cells. On the other hand, safrole, benzene and carbon tetrachloride were more recombinagenic in G1-arrested than in growing cells. Thus, inducibility of DEL recombination in G1-arrested cells parallels inducibility in G2-arrested cells making it less likely that sister chromatid recombination events might be involved. These data are discussed in terms of the mechanism of induced DEL recombination and the possible biological activities of these carcinogens.

UI MeSH Term Description Entries
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D012475 Salmonella A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.
D015825 Chromosomes, Fungal Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell. Chromosome, Fungal,Fungal Chromosome,Fungal Chromosomes
D016193 G1 Phase The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors. First Gap Phase,G1a Phase,G1b Phase,Gap Phase 1,First Gap Phases,G1 Phases,G1a Phases,G1b Phases,Gap Phase, First,Gap Phases, First,Phase 1, Gap,Phase, First Gap,Phase, G1,Phase, G1a,Phase, G1b,Phases, First Gap,Phases, G1,Phases, G1a,Phases, G1b

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