Effect of sulfite on the covalent reaction of benzo[a]pyrene metabolites with DNA.
Sulfur dioxide (SO2) potentiates the carcinogenicity of polycyclic aromatic hydrocarbons. To investigate the mechanism of SO2 cocarcinogenesis, the effect of sulfite, the hydrated form of SO2, on the covalent reaction of benzo[a]pyrene (BaP) metabolites with DNA in vitro was measured. [14C]BaP was incubated with rat lung or liver post-mitochondrial supernatant (S9), an NADPH generating system, calf thymus DNA and sodium sulfite (0-20 mM). In the presence of lung S9, covalent reaction increased linearly from 0.66 to 1.20 pmol BaP metabolites per mg DNA with increasing sulfite concentrations. Addition of sulfite to rat liver S9 also increased BaP-DNA adduct formation with BaP-DNA adducts increasing from 80 to 120 pmol per mg DNA. Sulfite altered the amount and pattern of BaP metabolites formed by either lung or liver enzyme preparations. BaP was metabolized more extensively and the amount of water soluble BaP metabolites formed increased significantly with sulfite present. With lung S9, the amount of BaP-tetrols, diols, and phenols increased slightly. With liver S9, diol and phenol formation was significantly lower while tetrol formation was unchanged. Incubation of rat lung S9 with sulfite resulted in formation of glutathione S-sulfonate (GSSO3H), a known inhibitor of glutathione S-transferases mediating the conjugation of glutathione (GSH) and BaP epoxides. Our results suggest that sulfite may, by altering the overall metabolic activation and detoxication of BaP, or by reacting directly with DNA, subsequently affect the covalent reaction of BaP metabolites with DNA. These are offered as possible mechanisms to explain the cocarcinogenic effect of SO2.
Leung
K H
KH
Department of Pharmacology, Duke University Medical Center, Durham NC 27710.
Keller
D A
DA
Menzel
D B
DB
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013367:Submitochondrial Particles / Q000378:metabolism; D013447:Sulfites / Q000494:pharmacology*
D001580:Benzopyrenes; D013447:Sulfites; D004247:DNA; C025026:sodium sulfite