Specificity of arsenite in potentiating cytogenetic damage induced by the DNA crosslinking agent diepoxybutane

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Environmental and Molecular Mutagenesis; (United States)

DOI:https://doi.org/10.1002/em.2850190303· OSTI ID:6854309

Wiencke, J K ^[1]; Yager, J W ^[2]

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1. Univ. of California, San Francisco, CA (United States)
2. Electric Power Research Institute, Palo Alto, CA (United States)

In the present study, the induction of sister chromatid exchanges (SCEs) and chromosomal aberrations were measured in normal human lymphocytes treated with low concentrations of arsenite alone (0.5-2.0 [mu]M) and arsenite in combination with the potent DNA crosslinking agent diepoxybutane (DEB). Experiments were carried out with lymphocytes from blood donors with different sensitivities to SCE induction by DEB. Arsenite, beginning at concentrations as low as 1 [mu]M, increased SCE frequencies; chromosomal aberration frequencies were increased at 2 [mu]M of arsenite. DEB treatments alone increased SCE frequencies and chromosomal aberrations. The yields of chromatid deletions and exchanges in lymphocytes exposed to both arsenite and DEB were markedly increased above the levels expected if the effects of the two agents had been simply additive. The frequencies of chromatid deletions were 4- to 8-fold greater than expected and chromatid exchanges were increased 7- to 40-fold. Chromatid exchanges detected in cells treated with arsenite and DEB were predominantly incomplete exchanges. The most dramatic increases in chromatid aberrations were observed in lymphocytes from an individual sensitive to SCE induction by DEB, indicating that individuals may vary in their sensitivity to the co-clastogenic effects of arsenite. At concentrations that dramatically affect aberrations, arsenite had no effect on the induction of SCEs by DEB. These studies suggest a specific interaction of arsenite with the induction or repair of DNA damage produced by DEB that leads to chromosomal aberrations but not to SCEs. Based on the selective chemical reactivity of low concentrations of arsenite with proteins containing vicinal dithiols and the occurrence of these groups within DNA repair proteins, it is proposed that the specific co-clastogenic effects of arsenite may be mediated by its interference with DNA repair activities. 39 refs., 1 fig., 1 tab.

• DOE Contract Number: AC03-76SF01012
• OSTI ID: 6854309
• Journal Information: Environmental and Molecular Mutagenesis; (United States), Journal Name: Environmental and Molecular Mutagenesis; (United States) Vol. 19:3; ISSN 0893-6692; ISSN EMMUEG
• Country of Publication: United States
• Language: English

Related Subjects

550400 -- Genetics
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKANES
ARSENIC COMPOUNDS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BUTANE
DNA REPAIR
EPOXIDES
GENETIC EFFECTS
HYDROCARBONS
INTERFERENCE
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
REPAIR
SYNERGISM