Mutagenicity and induction of sister chromatid exchange by optically active enantiomers of secondary butyl methanesulfonate

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Environmental and Molecular Mutagenesis; (USA)

DOI:https://doi.org/10.1002/em.2850130203· OSTI ID:7005926

Ball, J C; Salmeen, I T ^[1]; Morris, S M ^[2]

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1. Ford Motor Co., Dearborn, MI (USA)
2. National Center for Toxicological Research, Jefferson, AK (USA)

This report describes experiments in which a chiral alkyl methanesulfonate was used to investigate possible mechanisms by which alkylating agents cause their mutagenic, cytotoxic, and clastogenic effects. Optically active enantiomers and the racemic mixtures of 2-butyl methanesulfonate (2-BMS) were cytotoxic and mutagenic in Chinese hamster V79 cells and in AS52 cells and mutagenic in Salmonella typhimurium strains TA100 and TA1535. Within the experimental uncertainties, the cytotoxicity and mutagenicity curves were the same for the R and S enantiomers and for the racemic mixture. The 2-BMS isomers were cytotoxic and induced sister chromatid exchanges (SCE) in CHO-K{sub 1}-BH{sub 4} cells. The cytotoxicity curve was similar to that observed with V79 and AS52 cells. The results can be interpreted two ways. The first interpretation is that 2-BMS reacts via a carbocation, and the second interpretation involves an S{sub N}2 reaction of 2-BMS with DNA. The latter interpretation suggests that the mechanisms of mutagenesis, cytotoxicity, or the induction of SCE cannot distinguish between small (four-carbon) optically active DNA adducts. The authors favor the second interpretation because of solvolysis experiments showing the complete inversion of configuration of optically active 2-octyl methanesulfonate. While they assume that optically active 2-BMS will react using the same mechanism as chiral 2-OMS, they cannot exclude the possibility that 2-BMS reacts via a carbonation intermediate.

• OSTI ID: 7005926
• Journal Information: Environmental and Molecular Mutagenesis; (USA), Vol. 13:2; ISSN 0893-6692
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
SISTER CHROMATID EXCHANGES
DOSE-RESPONSE RELATIONSHIPS
SULFONIC ACID ESTERS
GENETIC EFFECTS
ALKYLATING AGENTS
ENANTIOMORPHS
ESCHERICHIA COLI
FIBROBLASTS
GUANOSINE
HAMSTERS
MUTAGENESIS
SALMONELLA TYPHIMURIUM
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BACTERIA
BIOLOGICAL EFFECTS
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
ESTERS
HETEROCYCLIC COMPOUNDS
MAMMALS
MICROORGANISMS
MUTATIONS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
RIBOSIDES
RODENTS
SALMONELLA
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology