Inhibition of rat methylbenzylnitrosamine metabolism by dietary zinc and zinc in vitro.

Abstract:

:Methylbenzylnitrosamine is an esophageal-specific carcinogen in the rat, and the incidence of methylbenzylnitrosamine-induced esophageal carcinoma is increased by dietary zinc deficiency. Methylbenzylnitrosamine requires activation by cytochrome P-450 to be mutagenic; the present study examined the role of dietary zinc deficiency and the in vitro addition of zinc on the cytochrome P-450-dependent microsomal metabolism of methylbenzylnitrosamine. Dietary zinc deficiency significantly increased the cytochrome P-450-dependent esophageal and hepatic microsomal metabolism of methylbenzylnitrosamine. These changes occurred without alteration in the specific content of total microsomal cytochrome P-450 of the esophagus or liver. The addition of zinc in vitro, at concentrations found in normal tissues, irreversibly inhibited the esophageal and hepatic cytochrome P-450-dependent microsomal metabolism of methylbenzylnitrosamine. These results suggest that physiological levels of zinc may be an endogenous inhibitor of methylbenzylnitrosamine metabolism. Dietary zinc deficiency appears to reduce this inhibition of cytochrome P-450 activity, resulting in an increase in carcinogen activation.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Barch DH,Fox CC,Rosche WA,Rundhaugen LM,Wrighton SA

doi

10.1016/0016-5085(92)90009-n

keywords:

subject

Has Abstract

pub_date

1992-09-01 00:00:00

pages

800-6

issue

3

eissn

0016-5085

issn

1528-0012

pii

0016-5085(92)90009-N

journal_volume

103

pub_type

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