In vitro stimulation of microsomal diethyl nitrosamine deethylase activity by vitamin K3 (menadione).

Vitamin K3 (menadione) has been found to stimulate diethyl nitrosamine (DEN)-deethylase activity in rat liver microsomes. The vitamin also takes care of the inhibitory effect of the anaerobic conditions as well as those of cytochrome poisons like sodium azide and sodium cyanide, possibly through production of active oxygen species. The enzyme was also stimulated by H2O2 and SOD and inhibited by catalase, thereby suggesting that H2O2 or some derivatives of it may be the active oxygen species involved in the reaction.

Effects of ovulen-50, diethylnitrosamine and phenobarbital on liver regeneration in female rats.

Short term effects of ovulen-50, a combination type oral contraceptive agent and phenobarbital—an established hepatic tumour promoter, were examined in the livers of diethylnitrosamine-initiated and uninitiated female rats. Liver mitotic activity as judged by liver weight, [3H] thymidine incorporation into DNA and levels of DNA, RNA and protein were measured in non-regenerating and regenerating liver. Hepatic γ-glutamyl transpeptidase activity and hepatocyte agglutination with concanavalin A were examined in diethylnitrosamine- and/or phenobarbital-treated rats. The results indicate that diethylnitrosamine or ovulen-50 individually are mitoinhibitory in regenerating liver. Phenobarbital alone has a slight mitostimulatory effects in nonregenerating liver, but no effect on liver regeneration. Administration of ovulen-50 and phenobarbital to diethylnitrosamine initiated rats mitigated the mitoinhibition during regeneration. Contrary to the earlier observation with ovulen-50, neither phenobarbital nor diethylnitrosamine induced hepatocyte agglutination in the presence of concanavalin A. Like ovulen-50, diethylnitrosamine also increased the level of hepatic γ-glutamyl transpeptidase. Phenobarbital produced only insignificant rise and did not substantially exacerbate the effect diethylnitrosamine. The data show that though some of the effects of ovulen-50 resemble those of diethylnitrosamine or phenobarbital, the changes observed may not be related to the neoplastic phenomenon since they were not seen in an initiator-promoter combination regimen.