Hydrocortisone affects the N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in Sprague-Dawley rats.
The effects of hydrocortisone on the in vivo acetylation of 2-aminofluorene (AF) and AF-DNA adducts in Sprague-Dawley rats were investigated. Pretreatment with hydrocortisone (50 mg/kg) 48 hours prior to the administration of AF (50 mg/kg) resulted in a 61% and 30% increase, respectively, in the urinary and fecal recovery of N-acetyl-2-aminofluorene (AAF) and a 36% increase in the metabolic clearance of AF to AAF. Hydrocortisone did not affect Michael's-Menten parameters for N-acetyltransferase (NAT) activity in blood, liver, lung and bladder. Similarly, the apparent value of Km for AF in the examined tissues was not affected by hydrocortisone. However, the apparent value of Vmax for liver NAT activity was significantly increased after hydrocortisone pretreatment. Following exposure of rats to AF with and without pretreatment with hydrocortisone, DNA-AF adducts were examined in the target tissue of liver and bladder and also in non-target tissue of lung and circulating leukocytes. The DNA-AF adducts in liver, bladder, lung and leukocytes were increased by pretreatment with hydrocortisone.
Chung
Jing-Gung
JG
Department of Microbiology, China Medical College and Hospital, Taichung, Taiwan, Republic of China. jgChung@mail.cmc.edu.tw
Chen
Guang-Wei
GW
Yang
Mei-Due
MD
Wang
Der-Yean
DY
Hung
Chi-Fu
CF
Lin
Wen-Chuan
WC
Chang
Huei-Ling
HL
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D004357:Drug Synergism; D005449:Fluorenes / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
C052668:2-aminofluorene-DNA complex; D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes; C012177:2-aminofluorene; D004247:DNA; D001191:Arylamine N-Acetyltransferase; D006854:Hydrocortisone