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.
Chung
J G
JG
Department of Microbiology, China Medical College, Taichung, Taiwan, Republic of China.
Chang
H L
HL
Yeh
C C
CC
Lu
H F
HF
Chang
C C
CC
Tsai
H D
HD
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000107:Acetylation / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004347:Drug Interactions; D005243:Feces / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D007369:Interferon Inducers / Q000494:pharmacology*; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013994:Tilorone / Q000494:pharmacology*; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
C052668:2-aminofluorene-DNA complex; D000276:Adjuvants, Immunologic; D018736:DNA Adducts; D005449:Fluorenes; D007369:Interferon Inducers; C012177:2-aminofluorene; D015073:2-Acetylaminofluorene; D001191:Arylamine N-Acetyltransferase; D013994:Tilorone