This analysis explored contributions of genotype (genes encoding enzymes linked to acrylamide and glycidamide metabolism) and smoking on hemoglobin adduct levels of acrylamide (AA), its metabolite glycidamide (GA), and their ratio (GA/AA). Acrylamide has been shown to be genotoxic in animal studies. Human exposure occurs from diet, tobacco smoke, and occupational exposure. Blood samples from 39 consenting acrylamide industry workers with low potential risk for work contact with acrylamide were used. Variants of EPHX1 Y113H EX6+5C>T and GSTP1 I105V EX5-24A>G and gene deletions in GSTM1 and GSTT1 were identified by PCR. Hemoglobin adducts were measured by HPLC-MS/MS. Urinary cotinine was measured by immunoassay as a proxy for smoking (i.e., cotinine >= 200ng/ml). Mean GA/AA ratios were calculated for dichotomized categories of EPHX1 (C/C + C/T=0.80, T/T=0.91), GSTP1(A/G + G/G=0.88, A/A=0.87), GSTM1 (null=0.92, present=0.85), and GSTT1 (null=0.69, present= 0.93). Separate linear regression models were run for log AA, GA, and GA/AA for each of these genotypes, with and without smoking adjustment. Smoking was highly significant when added to each model (p-values: 0.003 to <0.0001). EHPX1 T/T was significantly (p=0.04) associated with a higher GA/AA ratio after adjustment for smoking. The GSTT1 null genotype was significantly associated with lowered GA/AA ratios both before (p=0.0013) and after (p=0.0007) adjustment for smoking. The GSTT1 null genotype was also significantly associated with higher AA levels, before (P=0.02) and after (p=0.008) adjustment for smoking. Genotype approached significance with AA or GA in several models. Conclusion: GSTT1 genotype appeared to affect AA levels and the GA/AA ratio, while EPHX1 Y113H affected the GA/AA ratio after adjustment for smoking. Low sample size may have limited detection of other effects.
Physical-reactions; Risk-analysis; Risk-factors; Chemical-analysis; Chemical-reactions; Cell-biology; Cell-damage; Cellular-reactions; Genetic-factors; Genes; Genotoxic-effects; Genotoxicity; Animal-studies; Humans; Smoke-inhalation; Dietary-effects; Occupational-exposure; Work-environment; Chemical-factory-workers; Industrial-environment; Industrial-exposures; Mathematical-models
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina