Relationship between aromatic-DNA adduct levels and inducibility of the drug metabolizing enzyme aryl hydrocarbon hydroxylase in lymphocytes

Formation of promutagenic DNA adducts is thought to be a critical factor in the induction of various types of cancer. Since genetically determined differences in drug metabolizing enzyme activities might be associated with DNA adduct levels, we have determined aryl hydrocarbon hydroxylase (AHH) activity, glutathione S-transferase Ml (GSTM1) polymorphism, and aromatic-DNA adduct levels in 50 healthy subjects and 42 lung cancer patients. Both non-induced and 3-methylcholanthrene-induced AHH activities in peripheral mitogen-treated lymphocytes were detectable in all the samples. After controlling for the age, smoking status and season of the year, AHH inducibility was significantly higher in the patients than in the controls (P < 0.05). Surprisingly, in spite of a higher prevalence of smokers and higher median Brinkmann index (number of cigarettes smoked per day multiplied by number of years smoking) in the patient group, adjusted means of aromaticDNA adduct levels were similar in the controls and patients. Subjects with high AHH inducibility tended to have a larger odds ratio (OR) than those with low AHH inducibility while ORs seemed to be independent of GSTM1 polymorphism. This finding suggests that phase I enzyme AHH inducibility may be a more important contributor to aromatic-DNA adduct levels than GSTM1 polymorphism.