Esophageal cancer and microelements.
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.
Barch
D H
DH
Department of Medicine, University of Illinois, Chicago 60612.
D000818:Animals; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D006801:Humans; D009602:Nitrosamines; D051381:Rats; D014131:Trace Elements / Q000172:deficiency*; D015032:Zinc / Q000172:deficiency
D009602:Nitrosamines; D014131:Trace Elements; D015032:Zinc