Safrole-DNA adducts in human peripheral blood--an association with areca quid chewing and CYP2E1 polymorphisms.
It has been recently demonstrated that safrole (4-allyl-1,2-methylenedioxybenzene)-DNA adducts are present in oral cancer tissue from patients who have chewed areca quid (AQ) containing high concentration of safrole. In this study, the presence of safrole-DNA adducts in peripheral white blood cells from 88 subjects with a known AQ chewing history and 161 matched controls were studied with the aim of identifying the adducts as a biomarker for safrole exposure. This study also analyzed the correlation between the level of safrole-DNA adducts and polymorphism of the CYP2E1 gene, alone and in combination with the GST M1 and GST T1-deletion polymorphisms. The results demonstrated the presence of safrole-DNA adducts in 83 (94.32%) of the DNA samples from subjects with current AQ chewing history and 21 (13.04%) of the control samples without known AQ chewing habit ( [Formula: see text] ). Individuals with at least one CYP2E1 c2 allele had a significant higher frequency of safrole-DNA adducts (odds ratio (OR), 4.00; 95% confidence interval (CI), 1.03-15.53) than those with the CYP2E1 c1c1 genotype while chewing less than 20 areca quids per day. In conclusion, this study demonstrates the presence of safrole-DNA adducts in peripheral blood lymphocytes (PBL), and the presence of these safrole-DNA adducts is correlated with AQ chewing. In addition, the CYP2E1 would seem to play an important role in the modulation of safrole-DNA adduct formation.
Liu
Tsung-Yun
TY
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC.
Chung
Yu-Ting
YT
Wang
Pei-Feng
PF
Chi
Chin-Wen
CW
Hsieh
Ling-Ling
LL
D000328:Adult; D001114:Areca / Q000737:chemistry*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D017931:DNA Primers; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008409:Mastication; D010761:Phosphorus Radioisotopes; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012451:Safrole / Q000737:chemistry / Q000378:metabolism*
D018736:DNA Adducts; D017931:DNA Primers; D010761:Phosphorus Radioisotopes; D019392:Cytochrome P-450 CYP2E1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D012451:Safrole