title: Bioactivation and biotransformation of 1-nitropyrene in liver, lung and nasal tissue of rats.
abstract: 1-Nitropyrene (NP) is a known direct-acting bacterial mutagen and has been detected in the environment from such sources as diesel-exhaust emissions and coal-combustion fly ash. The purpose of this study was to investigate the mutagenic potential of NP in Salmonella typhimurium using rat liver, lung and nasal tissue as the enzyme-activating systems and to measure the rates of NP metabolism in these same tissues. Rat liver, lung and nasal tissue bioactivated NP to mutagens that were detected in the Ames bacterial test system. At all doses of NP and all protein concentrations of tissue S9, mutagenic responses were larger than that observed in the absence of any tissue. In both strains TA98 and TA100, about 1.0 mg/ml liver and nasal tissue S9 appeared to be the optimal concentration which resulted in the largest mutagenic response to NP, whereas 2.0 mg/ml of lung S9 was necessary to yield optimal responses. When NP was incubated with liver, lung or nasal tissue S9 and strain TA98 NR, mutagenic responses were significantly decreased when compared to the response seen in TA98. NP was metabolized to several oxidized metabolites (3-, 6- and 8-hydroxynitropyrene) in all tissues examined. Total rates of formation of NP metabolites for nasal tissue, liver and lung S9 were 650, 300 and 60 pmoles/mg protein/min, respectively. These results suggest that the respiratory tract, in particular the nasal tissue, may be an important site for in vivo bioactivation of inhaled NP.
mesh_terms: D000818:Animals; D001711:Biotransformation; D008168:Lung / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009928:Organ Specificity; D011721:Pyrenes / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D009153:Mutagens; D011721:Pyrenes; C032668:1-nitropyrene