Abstract
Summary Monooxygenation of 1-(2-chloroethyl)-3-( trans -α - methylcyclohexyl) - 1 - nitrosourea (Methyl CCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the presence of NADPH and O 2 by liver microsomes prepared from normal and phenobarbital-induced rats and mice were compared. The rate of Methyl CCNU hydroxylation was about 20 to 30 per cent of the rate of CCNU hydroxylation. A NADPH cytochrome P-450 dependent denitrosation of Methyl CCNU to the parent urea was observed. Single doses of CCNU (7.5, 15 and 30 mg/kg body wt) administered to rats two weeks prior to sacrifice and preparation of liver microsomes resulted in a dose-related decrease in cytochrome P-450 content, ethylmorphine N -demethylase and nitroreductase activities. These decreases gave values of 57, 33 and 60 per cent respectively relative to controls at the 30 mg/kg body wt dose level. Similar experiments are reported for the effects of CCNU treatment in vivo on CCNU monooxygenation by microsomes. These results are discussed in relation to previous studies with procarbazine.
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