Paclitaxel affects the amounts of the N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in Sprague-Dawley rats.
BACKGROUND
The effects of paclitaxel on the in vivo distribution and the levels of N-acetylation of 2-aminofluorene (AF) and AF-DNA adducts in Sprague-Dawley (SD) rats were studied.


RESULTS
For in vivo examination, pretreatment with paclitaxel (50 mg/kg) 48 hours prior to the administration of AF (50 mg/kg) resulted in a 28% and 43% decrease, respectively, in the urinary and fecal recovery of N-acetyl-2-aminofluorene (AAF), and a 22% decrease in the metabolic clearance of AF to AAF. Paclitaxel did not affect the Michaelis-Menten parameters for N-acetyltransferase (NAT) activity in blood, liver, lung, colon and bladder. Similarly, the Km value for AF in the examined tissues was not affected by paclitaxel. However, the Vmax value estimate of liver NAT activity was significantly decreased after paclitaxel pretreatment. Following exposure of rats to AF with and without pretreatment with paclitaxel, DNA-AF adducts were examined in the target tissues, liver, colon and bladder, and also in non-target tissues, lung and circulating leukocytes. The DNA-AF adducts in the liver, bladder, lung, colon and leukocytes were decreased by pretreatment with paclitaxel.


CONCLUSIONS
This is the first finding to show that paclitaxel affects AF distribution and N-acetylation and DNA adduct in SD rats in vivo.
Lu
Ko-Hsiu
KH
Institute of Medicine, Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, Taiwan, Republic of China.
Cheng
Kwork-Chui
KC
Hsia
Te-Chun
TC
Lin
Keh-Liang
KL
Wu
Chih-Lung
CL
Chou
Ming-Chih
MC
Chung
Hng-Gung
HG
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D018736:DNA Adducts / Q000187:drug effects*; D004336:Drug Antagonism; D005449:Fluorenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C052668:2-aminofluorene-DNA complex; D000972:Antineoplastic Agents, Phytogenic; D018736:DNA Adducts; D005449:Fluorenes; C012177:2-aminofluorene; D001191:Arylamine N-Acetyltransferase; D017239:Paclitaxel