Relationship of dietary zinc to 6-mercaptopurine teratogenesis and DNA metabolism in the rat

Abstract

The possible interaction between the level of maternal dietary zinc and the teratogenic activity of 6-mercaptopurine was investigated. Pregnant Sprague-Dawley rats were fed diets, containing 9, 100 or 1,000 ppm zinc from day zero of pregnancy and were given a single intraperitoneal injection of 6-MP (55 mg/kg) on day 11. At term, females in the group fed 1,000 ppm zinc (a high intake) showed less pronounced effects on reproduction and embryogenesis than did those fed 9 ppm (marginally deficient) or 100 ppm (normal) zinc. Embryos examined on day 12 of gestation had similar concentrations of protein and RNA; however, the DNA content was lower and the incorporation of ³H-thymidine was greater in the drug treated groups than in non-drug treated controls These results indicate that 6-mercaptopurine is acting to alter embryonic DNA. metabolism and that high levels of dietary zinc may ameliorate some of the deleterious effects of this drug on embryonic and maternal toxicity.