POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN SMOKERS AND THEIR RELATIONSHIP TO MICRONUTRIENT LEVELS AND THE GLUTATHIONE-S-TRANSFERASE M1 GENOTYPE
POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN SMOKERS AND THEIR RELATIONSHIP TO MICRONUTRIENT LEVELS AND THE GLUTATHIONE-S-TRANSFERASE M1 GENOTYPE
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DOI：
10.1093/carcin/15.11.2449
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发表时间：
1994-11-01
期刊：
影响因子：
4.7
通讯作者：
SANTELLA, RM
中科院分区：
文献类型：
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作者：
GRINBERGFUNES, RA;SINGH, VN;SANTELLA, RM
63名男性吸烟者参加了一项横断面研究，以确定多环芳烃(PAH)-DNA加合物水平与维生素a、维生素C和维生素e的摄入量/血清水平之间是否存在负相关关系。多环芳烃-DNA加合物与胡萝卜素摄入量以及血清β -胡萝卜素水平之间的关系也被确定。收集空腹血液样本，检测循环单核细胞中的多环ah - dna加合物、血浆可替宁和血清维生素A、β -胡萝卜素、维生素C和维生素e水平。由于解毒酶谷胱甘肽s -转移酶M1 （GSTM1）的遗传缺乏与肺癌风险增加有关，因此还确定了GSTM1基因型。通过竞争性酶联免疫吸附试验（ELISA）分析PAH-DNA加合物表明，70%的受试者检测到加合物，平均为4.38加合物/10(8)个核苷酸（范围为1.00-24.1/10(8)）。使用Pearson方法来确定各种宿主变量与PAH-DNA加合物之间是否存在任何关联。以前，没有发现多环芳烃dna加合物与吸烟/天、包年、每日/终生焦油暴露或血浆可定宁水平之间的显著关联（Santella et al., carcingenesis, 13,2041 -2045, 1992）。PAH-DNA加合物与血清胆固醇调节的维生素E水平呈负相关（r = -0.25， P小于或等于0.05），与吸烟调节的维生素C水平呈负相关（r = -0.22， P小于或等于0.09）。GSTM1基因型分层表明，这些关联仅限于具有零基因型的受试者。加合物与血清胆固醇调节维生素E的关系在无基因型组显著（r = -0.38, P≤0.04），在有基因型组无显著（r = -0.12, P = 0.5）。同样，对于吸烟调整后的维生素C，无基因型受试者与加合物的关系（r = -0.35， P小于或等于0.06）强于存在GSTM1的受试者（r = -0.05, P = 0.77）。这些结果与先前流行病学研究的发现一致，即抗氧化微量营养素状态或GSTM1基因型与肺癌发病率之间存在显著的负相关。应该进行更多的研究来确认维生素E在多环芳烃dna加合物形成中的可能作用，并进一步探索维生素a、β -胡萝卜素和维生素C在调节加合物形成和肺癌风险方面的可能作用。
Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH-DNA adducts and intakes of carotene, as well as serum levels of beta-carotene, were also determined. Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH-DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts, with a mean of 4.38 adducts/10(8) nucleotides (range 1.00-24.1/10(8)). Pearson's method was utilized to determine whether any associations existed between the various host variables and PAH-DNA adducts. Previously, no significant associations were found between PAH-DNA adducts and cigarettes smoked/day, pack-years, daily/lifetime tar exposures or plasma cotinine levels (Santella et al., Carcinogenesis, 13, 2041-2045, 1992). PAH-DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r = -0.25, P less than or equal to 0.05) and with smoking-adjusted vitamin C serum levels (r = -0.22, P less than or equal to 0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r = -0.38, P less than or equal to 0.04), but not in those with the gene present (r = -0.12, P = 0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r = -0.35, P less than or equal to 0.06) than in those with GSTM1 present (r = -0.05, P = 0.77). These results are consistent with findings of prior epidemiological studies identifying significant inverse associations between anti-oxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible role for vitamin E in PAH-DNA adduct formation and to explore further the possible roles of vitamin A, beta-carotene and vitamin C in modulating adduct formation and lung cancer risk.