DNA Methylation of the CYP1A1 Promoter Region is Associated with Anti-tuberculous Drug-induced Hepatic Injury

CYP1A1 is a typical one-phase drug metabolizing enzyme, and imbalances of its expression may cause liver tissue damage. At present, few studies on CYP1A1 methylation and anti-tuberculosis drug-induced liver injury are available. Studying the relationship between CpG island methylation in the CYP1A1 promoter region and drug-induced liver injury is, therefore, of great importance. Anti-tuberculosis drugs induced hepatotoxicity in HL-7702 cells was investigated. Dehydrogenase activity was detected by a lactate dehydrogenase assay kit; superoxide dismutase (SOD) activity and malonaldehyde (MDA) concentration were detected by a total superoxide dismutase test kit and a malondialdehyde test kit. Genomic DNA and RNA were extracted from cells; Methylation was inhibited by treating HL7702 cells with 5-aza-2'-deoxycytidine (AZA), and the level was analyzed via the methylation-specific PCR (MSP) methods. The increases in the methylation rate of CpG islands in the CYP1A1 promoter region and expression of DNA methyltransferases (DNMTs). And then the CYP1A1 mRNA and protein expression decreased with cell damage, thus suggesting that elevated methylation of the promoter region of the CYP1A1 gene may affect its expression and could be associated with cell damage. After treatment of the cells with AZA, increases in methylation rate and DNMTs expression were reduced, CYP1A1 mRNA and protein levels increased, and cell damage was ameliorated; these results indicate that inhibition of methylation can reduce cell damage. The promoter region hypermethylation of the CYP1A1 gene were related to its low mRNA levels.