in a dimethylnitrosamine demethylase process in rat livers. Inhibition could happen on by interfering in demethylase conformations or by interfering in synthesis and/or degradation of demethylase. Experiments showed that the Km doesn't change after 3-MC treatment. This strongly indicates that enzyme affinity is not influenced by 3-MC. Instead, incubation with 3-MC leads to a decrease in the amount of enzyme activity. These results point towards inhibition of demethylase synthesis and/or induction of demetylase degradation. Unpublished observations of Venkatesan, Argus and Arcos suggest that demethylase synthesis inhibition is most plausible. A possible mechanism for this reaction is depicted in figure (2). 3-MC is metabolized, via epoxidation, hydrolysis and another epoxidation, to a very reactive epoxide. Epoxidations are realized by the enzyme cytochrome P450. The second epoxide is not hydrolysed immediately because it is localized next to a bay region, which shields the epoxide. This way, the metabolite is able to travel and bind to DNA in figure (2). The mechanism is derived from the binding mechanism of benzo[a]pyrene to DNA. This is likely because it is plausible that two polycyclic aromatic hydrocarbons are metabolized via the same pathway. Deoxyguanosine is used in the figure, since that base appears to be bound to Benzo[a]pyrene far more often than the other bases. There appears to be an equilibrium in 3-MC-free and 3-MC-bound. It is hard to determine how when the equilibrium is formed due to difficulties with radioactive measurements. A probable saturating dosis is thought to be around 40 mg 3-MC/kg. Research on the effect of 3-MC in rat uteri concludes that 3-MC acts as an estrogen antagonist. The sexhormone is, like 3-MC, a polycyclic aromatic hydrocarbon. 3-MC and estrogen bind to estrogenreceptors competitively, reducing the estrogen expression. Metabolism MC is metabolized by rat liver microsomes into oxygenated forms which alkylate DNA. These oxygenated metabolites bind to double-stranded and single-stranded. Empirical data show that MC tends to bind mostly to G-bases8. When injected in lung, kidney or liver tissue of rats, it appears that the liver is able to reverse the MC-binding to DNA. Lung and kidney tissue are not capable of doing this, which may explain why MC is more carcinogenic in lungs and kidneys than in the liver. To be carcinogenic, the MC metabolite has to be covalently bound to DNA. Therefore, it is necessary for MC to be oxygenated in order to carcinogenic. Injected MC does not move away from