In vitro effects of straight-chain alkanes (n-hexane through n-dodecane) on rat liver and lung cytochrome P-450.
To evaluate the effect of straight-chain alkanes on normal detoxication reactions, we studied the in vitro effect of the homologous series n-hexane through n-dodecane on two cytochrome P-450 (EC 1.14.14.1) enzyme activities. Benzo[a]pyrene hydroxylase (BaPOHase) and 7-ethoxycoumarin deethylase activities were measured in liver and lung microsomes of control and beta-naphthoflavone-treated rats. In the presence of 2 mM n-hexane through n-dodecane, liver BaPOHase activity decreased from 67% of control with n-dodecane to 21% of control with octane. Lung benzo[a]pyrene hydroxylase was insensitive to all tested alkanes at 2 mM. In the presence of 2 mM alkanes, liver 7-ethoxycoumarin deethylase activity decreased from 73% of control with n-octane to 28% with n-octane. Lung 7-ethoxycoumarin deethylase was also sensitive to the alkane series. In the presence of 2 mM alkane the greatest effect was obtained with n-octane and represented a 56% loss in activity. Alkane concentration-dependence measurements showed 0.02-0.20 mM as the sensitive region of the curve for n-octane with maximal loss of activity achieved at 0.20 mM. Liver ethoxycoumarin deethylase activity from beta-naphthoflavone-treated rats was less sensitive towards the reactive alkane, n-octane, than the activity from control rats. Double-reciprocal-plot analysis revealed the maximal velocity (Vmax) was decreased in the presence of 0.2 mM n-octane. Hence this hydrocarbon did not exert its effect solely as an alternate substrate. The data show the n-alkanes, n-hexane through n-dodecane, interfered with a normal detoxication pathway in a manner that was chainlength-dependent, tissue-specific, and dependent on the preexposure history of the animal.
D015660:7-Alkoxycoumarin O-Dealkylase; D000473:Alkanes; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000096:biosynthesis / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D000473:Alkanes; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001579:Benzopyrene Hydroxylase