Metabolism of phenanthrene by the rat and the guinea pig

The metabolism of phenanthrene has been studied in the rat and the guinea pig, with the aim of seeking evidence in whole animals of the formation of dihydrodiol epoxides and/or diepoxides as metabolic intermediates and of comparing the bivalent sulfur metabolites excreted by the two species. After the administration of phenanthrene (50 mg/kg, ip) to young adult male rats and guinea pigs, a series of oxygenated- and bivalent sulfur-containing metabolites were isolated and identified by GC and GC/MS. Thirty-four oxygenated metabolites were isolated after enzymatic hydrolysis of the urine samples from the rat, whereas only twenty-one were detected in guinea pig urine. The major metabolites in both species were identified as 9,10- and 1,2-dihydrodiols, indicating that both K-region and non-K-region pathways are highly operative in vivo. Several triols and tetrols were also isolated as urinary metabolites, suggesting that dihydrodiol epoxides and/or diepoxides are involved in the metabolism of phenanthrene by the rat and the guinea pig. Besides the oxygenated metabolites, seven methylthio metabolites were isolated from the neutral fraction of hydrolyzed rat urine, whereas only two were detected in guinea pig urine. The major methylthio metabolite excreted by each species was 9-hydroxy-10-methylthio-9,10-dihydro- phenanthrene. This was observed as a second-day metabolite in the rat, and its appearance was accompanied by 9-hydroxyphenanthrene. Acidic urinary metabolites derived from glutathione conjugates are species-dependent. The major metabolite in hydrolyzed rat urine was N-acetyl-S-(9-hydroxy-9,10-dihydro-10-phenanthryl)-L-cysteine. In the guinea pig, the major bivalent sulfur acid was S-(9-hydroxy-9,10-dihydro- 10-phenanthryl)mercaptoacetic acid, but N-acetyl-S-(9-hydroxy-9,10-dihydro- 10-phenanthryl) -L-cys teine was also present. The excretion of S-(9-hydroxy-9,10-dihydro-10-phenanthryl)mercaptoacetic acid by the guinea pig may be due to incomplete acetylation or to a combination of acetylation and deacetylation of cysteine or cysteinylglycine adducts.