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In vitro effects of straight-chain alkanes (n-hexane through n-dodecane) on rat liver and lung cytochrome P-450.

Rabovsky-J; Judy-DJ; Pailes-WH
J Toxicol Environ Health 1986 Jul; 18(3):409-421
The in-vitro effects of the homologous series of six through 12 carbon straight chain alkanes (abbreviated nC6 through nC12) on two cytochrome-P-450 enzyme activities, benzo(a)pyrene-hydroxylase (BAP- hydroxylase) and 7-ethoxycoumarin-deethylase activities were investigated in liver and lung microsomes of control and beta- naphthoflavone (6051872) (BNF) treated rats. Male Sprague-Dawley- rats were intraperitoneally injected with 80 milligrams/kilogram BNF, 24 hours before sacrifice and liver and lung microsomes were prepared. Enzyme activities were measured in the presence of 0.002 to 2.0 millimolar (mM) alkane concentrations. In the presence of 2mM of one of the n-alkanes, liver BAP-hydroxylase activity decreased from 67 percent of control with the nC12 to 21 percent of control with the nC8 alkane. Lung BAP-hydroxylase was insensitive to all tested alkanes at 2mM. In the presence of 2mM alkanes, liver 7-ethoxycoumarin-deethylase activity decreased from 73 percent of control with the nC12 to 28 percent with the nC8 alkane. In the presence of 2mM alkane, the greatest effect on lung 7-ethoxycoumarin was obtained with the nC8 alkane, a 56 percent loss in activity. Alkane concentration dependence measurements showed 0.02 to 0.20mM as the sensitive region of the curve for the nC8 alkane with maximal loss of activity achieved at 0.2mM. Liver ethoxycoumarin-deethylase activity from BNF treated rats was less sensitive towards the reactive nC8 alkane, n-octane (111659), than the activity from control rats. The maximal velocity was decreased in the presence of through nC12, interfere with a normal detoxication pathway in a chain length dependent, tissue specific manner which is also dependent on pre exposure history.
NIOSH-Author; Organic-solvents; In-vitro-studies; Liver-microsomal-enzymes; Aliphatic-hydrocarbons; Liver-microsomal-metabolism; Cell-metabolism; Microsomal-enzymes
6051-87-2; 111-65-9
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Journal of Toxicology and Environmental Health