Modification Of Metabolic Gene Polymorphisms On 1-hydroxypyrene Excretions In Human Urine After Exposure To Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that are formed during the incomplete burning of organic substances. Some of them have been proved to be carcinogenic. Human exposure routes include respiratory inhalation, gastrointestinal and dermal intake. The metabolites of PAHs have been recommended into the risk assessment to take into account of exposure by all routes. We measured urinary 1-hydroxypyrene (1-OHP) concentrations in 447 coke oven workers (COWs) and 328 non-occupational exposed individuals, and explored the relationship with PAHs pollution in the breathing air, respirator usage, smoking and cooking style in the daily life. The population has also been genotyped in order to explore the effects of metabolic gene polymorphisms on urinary 1-OHP excretions after exposure to PAHs.We found urinary 1-OHP concentration has a good linear correlation with the sum of 16 PAHs recommended by US EPA, Benzo[a]pyrene (BaP), Pyrene (Pyr) and Dibenz[a,h]anthracene (DahA) in coke oven workers (r~2 > 0．5, P < 0．001) . The geometric mean of 1-OHP (μmol/mol creatinine) in post-shift urine in COWs was significantly higher than local non-occupational exposed individuals (Coking plantⅠ: 5．18 vs. 0．34; Coking plantⅡ4．21 vs. 0．19; P < 0．001) . Urinary 1-OHP concentrations in COWs were related to job categories and were degraded as Topside workers > Sideoven workers > Other COWs. This trend was similar to the results of PAHs concentrations in the air determined by random selected samples. Respirator usage (Yes or No) could significantly reduce 1-OHP excretions in urine (3．42 vs. 5．66, P = 0．020) . Heavy cigarette smoking could significantly enhanced 1-OHP excretions in uinre compared to nonsmokers (4．95 vs. 4．01, P = 0．068) . For the modifications of genotypes on urinary 1-OHP concentrations in COWs, it was found that AhR R554K AA carriers had a higher 1-OHP excretion in urine than GG carriers (5．12 vs. 4．20, P = 0．236) , UGT1A1-3263T>G GG carriers had a lower 1-OHP excretion than TT (3．92 vs. 5．11, P = 0．133) , GSTP1 I105V GG carriers had a lower 1-OHP excretion than AA carriers (2．91 vs 4．93, P = 0．087) . These three polymorphisms had significant effects on urinary 1-OHP concentrations in linear regression models after controlling the effects of other confounders including job categories, respirator usage and cigarette smoking (P = 0．064, 0．050 and 0．037, respectively). Univariate tests found that urinary 1-OHP concentrations could be influenced by AhR, CYP1A1, CYP1A2, CYP1B1, UGT1A1, GSTP1 and GSTP1 polymorphisms when taking into account of some two-way gene-gene interactions.We also measured urinary 1-OHP concentrations in 220 males and 108 females from a wire rod mesh plant without occupational exposure to PAHs. It was found that females had a higher 1-OHP excretion in urine compared to males (0．50 vs 0．34, P < 0．001) . Urinary 1-OHP concentrations in females were related to cooking frequency in the kitchen and the usage of cooking fume extractor during cooking in the linear regression model (P = 0．034 and 0．072, respectively), but active cigarette smoking habits and cooking frequency in the kitchen in males (P = 0．001 and 0．016, respectively). These results indicate that smoking and cooking are two main sources of exposure to PAHs in Chinese families.For the modifications of genotypes on urinary 1-OHP concentrations in non-occupational exposed individuals, it was found that AhR R554K AA carriers had a higher 1-OHP excretion in urine than GG carriers (0．49 vs 0．35, P = 0．054) , CYP1A2-163C>A AC carriers had a lower 1-OHP excretion than AA carriers (0．34 vs 0．44, p = 0．079) , EPHX1 EX1-362G>A AA carriers had a higher 1-OHP excretion than GG carriers (0．50 vs 0．36, P = 0．056) . These three polymorphisms had significant effects on urinary 1-OHP concentrations in linear regression models after controlling the effects of other confounders including sex, cigarette smoking and cooking activities (P = 0．062, 0．051 and 0．058, respectively). Univariate tests found that urinary 1-OHP concentrations could be influenced by AhR, CYP1A1, CYP1A2, CYP1B1, EPHX1 and UGT1A1 polymorphisms when taking into account of some two-way gene-gene interactions.In conclusion, we found that 1-OHP in urine could be a good biomarker for assessing recent exposure to PAHs in both occupational environment and non-occupational environment. Urinary 1-OHP concentrations could be modulated by gene polymorphisms. Our data on the modulations of metabolic gene polymorphisms on 1-OHP excretions in urine after exposure could help us to understand the mechanism of PAHs metabolism and find the biomarker of susceptibility, which is useful for us to recognize the susceptible individuals in the primary prevention of PAHs-induced diseases including cancers.