Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells
- Univ. of Kansas Medical Center, Kansas City, KS (United States)
Sulfur dioxide (SO[sub 2]) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO[sub 2], in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [[sup 3]H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [[sup 3]H]-anti-BPDE-derived products bount to protein; however, binding to nuclear DNA increase by more than 200% with 10 mM sulfite. Analysis of the supernatents from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c- sulfonate (BPT-10-sulfonate). [[sup 3]H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly. Once formed, this compound may be unable to leave the cell. The observed intracellular formation of BPT-10-sulfonate, a more stable DNA-modifying BaP derivative than BPDE and one which probably cannot leave the cell, could be responsible for this extended time course of nuclear localization and DNA modification.
- OSTI ID:
- 6788709
- Journal Information:
- Environmental Health Perspectives; (United States), Vol. 102:2; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
CARCINOGENESIS
PROTEINS
FRACTIONATION
SULFUR DIOXIDE
BIOCHEMICAL REACTION KINETICS
RESPONSE MODIFYING FACTORS
AROMATICS
CHALCOGENIDES
CONDENSED AROMATICS
HYDROCARBONS
KINETICS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PATHOGENESIS
REACTION KINETICS
SEPARATION PROCESSES
SULFUR COMPOUNDS
SULFUR OXIDES
560300* - Chemicals Metabolism & Toxicology
550200 - Biochemistry