Effects of the immunomodulator tilorone on the acetylation of 2-aminofluorene and DNA-2-aminofluorene adducts in the rats.

The present studies were undertaken to determine the effect of tilorone dihydrochloride (a synthetic interferon inducer) on the in vivo acetylation of 2-aminofluorene and DNA-2-aminofluorene adducts. For in vivo examination, pretreatment with tilorone dihydrochloride (50 mg/kg) 48 hr prior to the administration of 2-aminofluorene (50 mg/kg) resulted in a 35% and 29% increase in the fecal and urinary recovery of N-acetyl-2-aminofluorene and a 52% increase in the metabolic clearance of 2-aminofluorene to N-acetyl-2-aminofluorene. Following the exposure of rats to the 2-aminofluorene with or without pretreatment with tilorone dihydrochloride, DNA-2-aminofluorene adducts were determined in liver, bladder, lung and also in circulating leukocytes. The DNA-2-aminofluorene adducts in liver were increased by pretreatment with tilorone dihydrochloride. This is the first demonstration of tilorone-induced increasing in N-acetylation of carcinogens and DNA-carcinogen adducts in vivo.