ESOPHAGEAL MICROSOMAL METABOLISM OF N-NITROSOMETHYLBENZYLAMINE IN THE ZINC-DEFICIENT RAT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5629-5633
Abstract
Epidemiological studies in China suggest that dietary Zn deficiency and environmental exposure to N-nitrosamine carcinogens, such as N-nitrosomethylbenzylamine (NMBA), are among the factors associated with an increased incidence of esophageal carcinoma in humans. NMBA belongs to a class of nitrosamines which require activation by the cytochrome P-450-dependent mixed-function oxidases in order to be mutagenic. Rats maintained on a Zn-deficient diet exhibited an increased incidence of NMBR-induced esophageal carcinoma when compared to rats on a control diet. The increased tumor formation was associated with an alteration of the microsomal metabolism of NMBA. Weanling male Sprague-Dawley rats were raised on egg protein diets containing 2.3 ppm Zn (low Zn) or 50 ppm Zn (control Zn). Analysis of tissues revealed a rapid decline in the levels of Zn in serum and esophagi of the animals fed the low-Zn diet. Gastric and hepatic Zn content did not differ significantly between the animals fed the low-Zn diet and the animals fed the control Zn diet, even after 6 wk. Microsomes were prepared from esophageal mucosa, livers, and forestomachs from weanling animals fed these diets for 3 wk. The rate of formation of benzaldehyde from NMBA by esophageal mucosal microsomes prepared from the rats fed the low-Zn diet was nearly 10-fold higher than that of the rats fed the control Zn diet [0.230 .+-. 0.047 (SE) vs. 0.024 .+-. 0.008 nmol/min per mg microsomal protein; P < 0.001]. The rate of benzaldehyde formation by hepatic microsomes was 0.062 .+-. 0.005 nmol/min per mg microsomal protein in the rats fed the low-Zn diet and 0.042 .+-. 0.002 nmol/min per mg microsomal protein in the rats fed the control Zn diet (P < 0.01). The rate of benzaldehyde formation by forestomach microsomes were not detectable in tissue from rats on either diet. This increased rate of NMBA metabolism by esophageal mucosal microsomes from the Zn-deficient rats may explain the increased incidence of esophageal carcinoma in these animals. [Implication with respect to origin of dietary nitrosamines in fungal food contamination were presented.].

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