DNA ethylation in hamster tissues during subchronic diethylnitrosamine administration and in the hamster trachea after acute diethylnitrosamine administration.

Abstract

Formation of O6-ethylguanine (O6EG) in trachea DNA was measured 12 h after acute i.p. administration of 50, 100 and 200 mg diethylnitrosamine (DEN)/kg body wt to Syrian golden hamsters. Purine bases were fractionated by h.p.l.c., and ethylated guanines were quantified optically by fluorescence spectrophotometry. Significant levels of this promutagenic base were found after the various single doses of DEN. O6EG in trachea DNA was also measured at various times up to 48 h after an acute i.p. dose of 200 mg DEN/kg body wt. The maximum level of O6EG was detected 12 h after DEN treatment. A rapid decrease in O6EG concentration was seen in trachea DNA between 12 and 24 h, but only a negligible decrease was detected from 24 to 48 h post-treatment. The formation and accumulation of O6EG in trachea, liver, lung and kidney DNA were determined in hamsters treated subchronically with DEN, 20 mg/kg body wt, s.c. twice weekly up to 8 weeks. O6EG accumulated to significant levels in trachea and liver DNA. 7-Ethylguanine did not accumulate in the DNA of any of the organs studied during subchronic DEN exposure. The formation and persistence of O6EG in trachea DNA of DEN-treated hamsters correlated with the sensitivity of this tissue to the carcinogenic action of DEN.