Oral administration of 5-methoxypsoralen affects the distribution and metabolism of 2-aminofluorene in Sprague-Dawley rats.
BACKGROUND
The effects of 5-methoxypsoralen (5-MOP) on the distribution and metabolism of chemical carcinogens such as 2-aminofluorene (AF) has not been previously reported. In this study, the influences of 5-MOP on the metabolism of AF in Sprague-Dawley (SD) rats were investigated.


METHODS
After receiving 5-MOP in 24 hours, AF was introduced into each animal by gastric intubation. After 12, 24, 48 and 72 hours the urine, feces, and cytosol of the liver, kidneys, stomach, colon, bladder and blood of rats were collected and assayed for AF and its metabolites by HPLC.


RESULTS
Compared to the control regimen, 5-MOP caused an increase of the metabolites excreted in urine and feces. The largest dose of metabolites were excreted between 48-72 hours. The major metabolite excreted in the urine was 9-hydroxy-AAF (9-OH-AAF) and in the feces was 7-hydroxy-AAF (7-OH-AAF). There was no time-effect for the tissues, and the liver was the main target organ for the AF and its metabolites. The major residual metabolite of AF in the liver, kidneys, stomach, colon and bladder was 7-OH-AAF. In blood it was 9-OH-AAF. The bladder had the lowest metabolic residue in tissues, and blood played the role of transportation but was not the target organ. 5-MOP decreased the concentration of AF and its residual metabolites of liver, stomach, kidneys, bladder and blood at various times.


CONCLUSIONS
5-MOP increased the metabolism of AF in order to transform to ring-hydroxylated metabolites and increased excretion of the ring-hydroxylated metabolites, therefore decreasing AF and its residual metabolites in vivo. Although 5-MOP was shown to be an inhibitor of CYP 2A6 and CYP 2B1, somehow it causes an increase of activity in AF metabolism in vivo; it induces more CYPs involved in the metabolism of AF.
Lee
Yi-Min
YM
Department of Medical Technology, Chungtai Institute of Health Sciences and Technology, Taichung, Taiwan, 406, Republic of China.
Chen
Shan-Fu
SF
Li
Yu-Ching
YC
Lin
Song-Shei
SS
Chung
Jing-Gung
JG
D000078223:5-Methoxypsoralen; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005449:Fluorenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D014018:Tissue Distribution / Q000187:drug effects
D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene; D000078223:5-Methoxypsoralen; D008730:Methoxsalen