Effect of nutritional zinc-deficiency on O6-alkylguanine-DNA-methyl-transferase activities in rat tissues.

The effect of nutritional zinc-deficiency on the activities of O6-alkylguanine:DNA methyltransferase (AGT) in 9 rat tissues including liver, lung, kidney, spleen, brain, esophagus, forestomach, gastric-stomach and small intestine has been examined. Individual tissue extracts prepared from zinc-deficient and pair-fed, zinc-sufficient rats were incubated with N-[3H]methylnitrosourea-methylated calf thymus DNA for 1 h. The activities of AGT in these tissues were measured by two methods: (a) the transfer of the methyl group from O6-methylguanine in substrate DNA to AGT protein, and (b) the determination of the ratio of O6-methylguanine:7-methylguanine remaining in substrate DNA following incubation. AGT activities (expressed as fmol protein methylated/h per mg protein) were significantly reduced in the esophagus, spleen and lungs of zinc-deficient rats as compared to those in their corresponding zinc-sufficient counterparts. The ratio of O6-methylguanine:7-methylguanine was also reduced in the esophagus of the zinc-deficient rat. These results were consistent with our earlier findings that dietary zinc-deficiency enhances nitrosamine-induced esophageal carcinogenesis in rats.