The in vitro effects of alkanes, alcohols, and ketones on rat lung cytochrome P450-dependent alkoxyphenoxazone dealkylase activities.
Arch Toxicol 1989; 63(1):13-17
The effects of 21 aliphatic hydrocarbons on enzyme activities in lung microsomes from male Sprague-Dawley-rats were investigated. The specific enzymes considered were benzyloxyphenoxazone-dealkylase (BzOPhase) and ethoxyphenoxazone-dealkylase (EtOPhase). The rats were injected once with beta-naphthoflavone (BNF) at 80mg/kg 48 hours prior to sacrifice. The BzOPhase mediated release of resorufin was inhibited by the straight chain alkanes with 6 to 11 carbons. This inhibition was directed at the cytochrome-P450 dependent monooxygenase activity. Up to concentrations of 10 millimolar (mM) the straight chain alkanes did not affect EtOPhase activity. In branched heptane and hexane compounds the position of the methyl group affected the inhibiting potential with 3- methylheptane (589811), 4-methylheptane (589537) and 2,5- dimethylhexane (592132) causing 80 percent inhibitions. EtOPhase activity was not inhibited by the branched chain aliphatics. A decreased sensitivity of BzOPhase was demonstrated toward alcohol and carbonyl substituted hexanes. Some inhibitory potential was displayed toward the lung microsomal EtOPhase activity by 2-hexanol (626937) and 2-hexanone (591786). Octanols and octanones increased the 50 percent inhibition values toward BzOPhase compared to the unsubstituted normal octane. Octanol and octanone compounds inhibited EtOPhase activity as well.
NIOSH-Author; Liver-microsomes; Microsomal-enzymes; Enzyme-activity; Laboratory-animals; Environmental-contamination; Environmental-pollution; Lung-cells; Pulmonary-system-disorders; Alcohols; Ketones; Alkanes
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Archives of Toxicology