Metabolism of @entity107 by nasal mucosa and hepatic microsomes from hamster and XXXX : species specificity of nasal mucosa.

@entity4235 @entity108 @entity107 @entity109 @entity329 @entity105 @entity35 @entity22463 @entity3094
The oxidative metabolism of @entity107 ( @entity108 ) was investigated by @entity3094 determination using microsomes from nasal mucosa and liver of @entity35 and nasal mucosa and liver of @entity329 , to establish the role of metabolic activation in the organo-targets for the carcinogenicity of the @entity22463 . The hepatic microsomal de-ethylation of @entity108 followed simple and biphasic Michaelis-Menten kinetics for @entity35 liver and hamster liver, respectively. Both de-ethylations were inducible by @entity109 (PB) and the @entity108 -de-ethylase activities and the Michaelis constants were determined. Microsomes from hamster liver showed a higher metabolic rate (Vmax) and a better affinity (Km) towards @entity108 with respect to microsomes from @entity35 liver. In hamster, microsomes from nasal tissue biotransformed @entity108 at a rate and affinity quite similar to those of liver. In contrast, nasal mucosa of @entity35 metabolized @entity108 poorly. The effect of @entity4235 , a classical inhibitor of P-450 monooxygenases, on @entity108 de-ethylation was studied. It inhibited both hepatic and nasal @entity108 -de-ethylase activity, with greater affinity towards the latter. In addition @entity4235 had a greater inhibitory effect on the hepatic P-450 isozymes induced in PB-treated animals. These results correlate well with the organotrophy of @entity108 @entity105 in the nasal region of hamster, but not of @entity35 . They suggest that for the nose the metabolic activation of @entity108 in situ is necessary to elicit its carcinogenic effect.
