Investigations were undertaken to characterize the toxicity in
animals treated with 1, 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU).
Primary experimental interest in this compound had centered around
its antineoplastic activity; however, clinical application of the compound
resulted in the appearance of delayed toxicity symptoms. A
critical evaluation of the toxicity associated with BCNU has...
Rats were given single i.p. injections of BCNU to
investigate changes in hepatic cytochrome P-450 content and
specific activity in male rats. Microsomal P-450 levels
were unchanged from 6 hours to 7 days after BCNU treatment
but by day 21 they had decreased 45%. Ethylmorphine N-demethylase
activity (nm product x...
Three highly purified forms of cytochrome P-450 (P-450a, P-450b, P-450c) from Aroclor 1254-induced rat hepatic microsomes catalyzed the monooxygenation of 1-(2- chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and 1-(2-chloroethyl)-3-(cyclohexyl)-1-nitrosourea (CCNU) in the presence of purified NADPH cytochrome P-450 reductase, NADPH and oxygen. Cytochrome P -450- dependent monooxygenation of CCNU gave six alicyclic hydroxylation products...
Certain 2- chioroethyl nitrosoureas have been demonstrated
to be highly specific inactivators of chymotrypsin
in vitro and glutathione reductase, both in vivo and in
isolated rat hepatocytes. The inactivation of glutathione
reductase in isolated hepatocytes resulted in an increased
sensitivity toward an adriamycin induced oxidative
challenge.
Prolonged incubation of 1-(2-chloroethyl)-3-([1-¹⁴...