Reed G A
Carcinogenesis. 1987 Aug;8(8):1145-8. doi: 10.1093/carcin/8.8.1145.
Benzo[a]pyrene (BP) and sulfur dioxide (SO2) are ubiquitous air pollutants and are also components of tobacco smoke. Although SO2 itself is not carcinogenic, concurrent administration with BP results in enhancement of respiratory tract tumorigenesis. In biological systems, SO2 exists as its hydrated form, sulfite (SO3(2-) ). Sulfite readily undergoes autoxidation, generating potent oxidant species. When 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) is included in sulfite autoxidation mixtures it is converted to more polar products, most notably 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (BP tetraols). This implies the intermediacy of 7,8-dihydroxy-9,10-epoxy- 7,8,9,10-tetrahydro-benzo[a]pyrenes (BPDE). We report here the sulfite-dependent conversion of BP-7,8-diol to forms highly mutagenic to Salmonella typhimurium strain TA 98. This activation is observed at BP-7,8-diol concentrations of from 2 to 40 microM and at sulfite concentrations of from 0.5 to 10 mM. In the presence of 10 microM BP-7,8-diol, half-maximal activation is observed at 1.6 mM sulfite. Sulfite itself is neither toxic nor mutagenic to the bacteria under these conditions. The time course of the activation of BP-7,8-diol and its sensitivity to inhibition by antioxidants indicate a requirement for sulfite autoxidation. These data further support the sulfite-dependent epoxidation of BP-7,8-diol. Not only does sulfite convert this promutagen to its active mutagenic form, sulfite also enhances the mutagenic activity of BP diolepoxides toward the tester strain. The reversion frequency in response to 0.1-0.5 microM anti-BPDE is increased by up to 33% in the presence of 1 mM sulfite, and by up to 270% with 10 mM sulfite. The mechanism of this enhancement of anti-BPDE activity is not known, but could be related to inhibition of the glutathione-S-transferase system which has been previously reported for sulfite. These results are discussed in regard to the noted cocarcinogenicity of sulfur dioxide for BP.
苯并[a]芘（BP）和二氧化硫（SO₂）是普遍存在的空气污染物，也是烟草烟雾的成分。虽然SO₂本身不致癌，但与BP同时施用会导致呼吸道肿瘤发生增强。在生物系统中，SO₂以其水合形式亚硫酸盐（SO₃²⁻）存在。亚硫酸盐很容易发生自氧化，产生强氧化剂。当7,8 - 二羟基 - 7,8 - 二氢苯并[a]芘（BP - 7,8 - 二醇）包含在亚硫酸盐自氧化混合物中时，它会转化为极性更强的产物，最显著的是7,8,9,10 - 四羟基 - 7,8,9,10 - 四氢苯并[a]芘（BP四醇）。这意味着7,8 - 二羟基 - 9,10 - 环氧 - 7,8,9,10 - 四氢苯并[a]芘（BPDE）的中间作用。我们在此报告了亚硫酸盐依赖的BP - 7,8 - 二醇向对鼠伤寒沙门氏菌TA 98具有高度致突变性的形式的转化。在BP - 7,8 - 二醇浓度为2至40微摩尔/升以及亚硫酸盐浓度为0.5至10毫摩尔/升时观察到这种活化作用。在存在10微摩尔/升BP - 7,8 - 二醇的情况下，在1.6毫摩尔/升亚硫酸盐时观察到半最大活化作用。在这些条件下，亚硫酸盐本身对细菌既无毒也无致突变性。BP - 7,8 - 二醇活化的时间进程及其对抗氧化剂抑制的敏感性表明需要亚硫酸盐自氧化。这些数据进一步支持了亚硫酸盐依赖的BP - 7,8 - 二醇环氧化作用。亚硫酸盐不仅将这种前诱变剂转化为其活性诱变形式，还增强了BP二环氧物对测试菌株的诱变活性。在存在1毫摩尔/升亚硫酸盐的情况下，对0.1 - 0.5微摩尔/升反式BPDE的回复频率增加高达33%，在存在10毫摩尔/升亚硫酸盐时增加高达270%。这种反式BPDE活性增强的机制尚不清楚，但可能与先前报道的亚硫酸盐对谷胱甘肽 - S - 转移酶系统的抑制有关。关于二氧化硫对BP的协同致癌性，对这些结果进行了讨论。
