Green J L, Jones B C, Reed G A
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Environ Health Perspect. 1994 Feb;102(2):216-20. doi: 10.1289/ehp.94102216.
Sulfur dioxide (SO2) 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 SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-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 after a 4-hr incubation period. The net 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 [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)
二氧化硫（SO₂）在呼吸道中可能与苯并[a]芘（BaP）起协同致癌作用。我们通过研究7r,8t - 二羟基 - 9t,10t - 环氧 - 7,8,9,10 - 四氢苯并[a]芘（反式 - BPDE）与亚硫酸盐（SO₂的生理形式）在小鼠呼吸道上皮细胞系（C10）中的相互作用，对这种效应进行了建模。我们将C10细胞暴露于[³H] - 反式 - BPDE，并测定了1 mM和10 mM亚硫酸盐对标记产物摄取和亚细胞定位的影响。放射自显影分析表明，孵育4小时后，亚硫酸盐使反式 - BPDE衍生物质的核定位增加了一倍。在最初的60分钟内，亚硫酸盐对反式 - BPDE衍生物质的净核定位没有影响，但在含亚硫酸盐的孵育过程中，整个4小时孵育期内核定位持续增加。60分钟后，在不含亚硫酸盐的孵育中，反式 - BPDE衍生物质的核定位几乎没有增加。进行亚细胞分级分离以确定与细胞质和细胞核部分相关的标记量，并确定与蛋白质和DNA的共价结合。亚硫酸盐使与蛋白质结合的[³H] - 反式 - BPDE衍生产物的量适度增加；然而，在10 mM亚硫酸盐存在下，与核DNA的结合增加了200%以上。对暴露于反式 - BPDE和亚硫酸盐的细胞的细胞质和细胞核部分的上清液分析表明存在7r,8t,9t - 三羟基 - 7,8,9,10 - 四氢苯并[a]芘 - 10c - 磺酸盐（BPT - 10 - 磺酸盐）。[³H] - BPT - 10 - 磺酸盐无法进入C10细胞，这表明它是在细胞内形成的。（摘要截断于250字）
