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2877662 
Journal Article 
Effect of CYP2E1 Ras I genotypes on CYP2E1 enzyme activity and DNA damage induced by phenol in immortalized human lymphocytes 
Fan Kai-Hong; Zhang Juan; Yin Li-Hong; Pu Yue-pu 
2007 
178-181 
WOS:000250819100109 
[Objective] The present study was to investigate the CYP2E1 enzyme activity and DNA damage of immortalized human lymphocytes with three different genotypes (wild, heterozygosis and mutant at 5'-flanking region Ras I of CYP2E1 gene) after exposure to phenol, an intermediate of benzene, with the purpose to explore the relationship among the genotypes of CYP2E1 Ras I, CYP2E1 gene function and bio-effects, as well as the toxic mechanisms of benzene. [Methods] The immortalized human lymphocytes with different genotypes were exposed to phenol at various doses for 24 to 72 hours. MTT assay was used to detect the cytotoxicity of phenol to lymphocytes. The activity of CYP2E1 enzyme was assessed by spectrophotography. The DNA damage of the lymphocytes. was assessed by single cell gel electrophoresis (SCGE). [Results] The cellular growth inhibiting effect was observed in immortalized human lymphocytes with three genotypes after 0.05% phenol exposure and the maximal no-effect concentration of phenol to human lymphocytes was 0.01%. The activity of CYP2E1 enzyme in the cells could be induced by 0.01% phenol exposure for 48h. The increasing rates of enzyme induction in wild, heterozygosis and mutant genotype cells were 81.79%, 56.28% and 25.51%, respectively. Effects of DNA damage were observed in the cells with each genotype exposed to 0.005% and 0.01% phenol and the most significant damage effect was present in the cells with wild genotype(P<0.05). A positive correlation was found between CYP2E1 enzyme activity and DNA damage of immortalized human lymphocytes exposed to phenol. [Conclusion] CYP2E1 enzyme activity and DNA damage of immortalized human lymphocytes induced by phenol were obviously influenced by genotypes of CYP2E1 Ras I site. The activity of CYP2E1 enzyme could be induced to the highest level and DNA damage was most severe in the wild genotype lymphocytes after exposure to phenol. Polymorphisms of CYP2E1 Ras I site might influence the effects of DNA damage induced by phenol by regulating CYP2E1 enzyme activity. So CYP2E1 Ras I wild genotype might be the susceptible gene for benzene toxicity. 
phenol; genotype; immortalized human lymphocytes; DNA damage; CYP2E1