Effects of cigarette smoking on human in vivo somatic mutation: Longitudinal sampling of smokers demonstrates a decrease in glycophorin A (GPA) allele-loss variant cell frequencies following cessation
- Lawrence Livermore National Lab., CA (United States)
- Univ. of California, San Francisco, CA (United States)
- Columbia Univ., New York, NY (United States)
The human in vivo glycophorin A (GPA) assay uses immunolabeling and flow cytometry to quantitate somatic variation in erythrocytes expressing GPA allele loss and allele-loss and duplication phenotypes in peripheral blood samples. The frequency of these variant erythrocytes (V[sub f]) presumably reflects the level of somatic mutation at this locus in the nucleated hematopoietic precursor cells of the bone marrow. We have previously shown that the GPA assay is a cumulative, integrating biodosimeter of accidental, medical, and occupational exposure to chemical mutagens and ionizing radiation. Surveys of otherwise unexposed populations point to an increased GPA allele loss V[sub f] in cigarette smokers compared to nonsmokers consistent with the induction of somatic mutation by mutagenic components of tobacco smoke. To further test this association, blood samples from active heavy smokers who entered a multi-endpoint Smokender study were obtained at enrollment and at 10 wks and 6 and 12 mo following smoking cessation. Results from the first 109 individuals reveal a decrease in the mean GPA allele loss V[sub f] ranging from 9.0 [+-] 1.0 [times] 10[sup [minus]6] (n = 109) for the active smoking samples, to 9.1 [+-] 1.8 [times] 10[sup [minus]6] (n = 46), 6.0 [+-] 0.7 [times] 10[sup [minus]6] (n = 15), and 5.8 [+-] 1.6 [times] 10[sup [minus]6] (n = 8) for the three postcessation samples, respectively. No change in the GPA allele loss and duplication V[sub f] was observed, thus confining the spectrum of mutational events induced by exposure to cigarette smoke. The observed decrease in the level of somatic mutation in smokers following cessation suggests limited persistence and/or repair of tobacco-smoke-induced genetic alterations consistent with epidemiologic findings of decreased cancer risk in smokers following cessation.
- OSTI ID:
- 7159041
- Journal Information:
- Journal of Toxicology and Environmental Health; (United States), Journal Name: Journal of Toxicology and Environmental Health; (United States) Vol. 40:2-3; ISSN 0098-4108; ISSN JTEHD6
- Country of Publication:
- United States
- Language:
- English
Similar Records
Biodosimetry of ionizing radiation in humans using the glycophorin A genotoxicity assay
Elevated somatic mutations at the glycophorin a (GPA) locus are associated with PAH exposure in Finnish iron foundry workers
Related Subjects
551000 -- Physiological Systems
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AEROSOLS
ANIMAL CELLS
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY FLUIDS
BONE MARROW CELLS
COLLOIDS
CONNECTIVE TISSUE CELLS
DISPERSIONS
ERYTHROCYTES
INDUCTION
IONIZING RADIATIONS
MATERIALS
MUTAGENESIS
MUTATIONS
RADIATIONS
REPAIR
RESIDUES
SMOKES
SOLS
SOMATIC CELLS
SOMATIC MUTATIONS
TOBACCO SMOKES