Journal of the American College of Nutrition, Vol 8, Issue 2 99-107, Copyright © 1989 by American College of Nutrition
Esophageal cancer and microelements
D. H. Barch
Department of Medicine, University of Illinois, Chicago 60612.
Epidemiological studies have identified dietary zinc deficiency,
methylbenzylnitrosamine, and ethanol as factors strongly associated with an
increased incidence of esophageal carcinoma in man. In addition, these
studies have identified other trace elements which may also affect the
incidence of esophageal carcinoma. Animal models have confirmed that
dietary zinc deficiency increases the incidence of
methylbenzylnitrosamine-induced esophageal carcinoma and that dietary zinc
deficiency also increases the incidence of other dialkylnitrosamine-induced
carcinomas. The dialkylnitrosamine carcinogens are activated by
NADPH-dependent cytochrome P-450 enzymes in their target tissues. The
activated methylbenzylnitrosamine methylates DNA, forming O6-methylguanine
adducts. These O6-methylguanine adducts can lead to point mutations in DNA,
and such mutations are known to be responsible for the induction of certain
carcinogen-induced tumors. We have demonstrated that dietary zinc
deficiency increased the cytochrome P-450-dependent microsomal metabolism
of methylbenzylnitrosamine and dimethylnitrosamine, two members of this
class of dialkylnitrosamine carcinogens, while the addition of zinc in
vitro noncompetitively inhibits the microsomal metabolism of these
carcinogens. We have also demonstrated that dietary zinc deficiency is
associated with an increased formation of O6-methylguanine in the
esophageal DNA of zinc-deficient animals treated with
methylbenzylnitrosamine. This increased formation of the mutagenic DNA
adduct O6-methylguanine may explain the increased incidence of
dialkylnitrosamine-induced carcinomas observed with dietary zinc
deficiency. Other trace elements, including molybdenum, selenium, and
magnesium, may also alter the incidence of esophageal carcinoma, but
studies of these elements are not as conclusive as the epidemiological and
experimental studies linking dietary zinc deficiency with an increased
incidence of human esophageal carcinoma.