In vivo evaluation of teratogenesis and cytogenetic changes following methylmercuric chloride treatment

Mercury is a major environmental pollutant and a proven teratogen in man and animals. Its teratogenicity and effects on fetal chromosomes were investigated in mice. Various dose levels of methylmercuric chloride (MMC) were administered via an intragastric tube to pregnant ICR Swiss/Webster mice on day 9 of gestation. On day 18 of gestation the animals were killed and the fetuses were removed. Fetal lung and liver tissues were processed for cytogenetic studies. Fetuses were also fixed in Bouin's solution for subsequent teratological examination by using Wilson's technique. Mercury levels were determined in maternal blood and randomly selected fetuses. One fetus from each litter was processed for skeletal staining with Alizarin Red S. A significant increase in embryonic deaths and resorptions was observed at all dose levels. The incidence of fetal anomalies was significantly increased following maternal treatment with 10, 15, or 20 mg/kg of MMC. Maternal weight between day 9 and day 18 of gestation decreased significantly. The LD50 of MMC in pregnant mice was determined to be 20 mg/kg of body weight; the LD100 was 30 mg/kg. A significant difference was observed between the mean fetal weights at the various dose levels. Levels of mercury were found to be significantly higher in treated animals and fetuses, and increased in a dose-related manner. The levels of mercury were significantly higher in the fetuses than in the mothers at the same dosage, indicating a correlation between the levels of mercury in maternal mice and corresponding higher levels in their fetuses. Cytogenetic studies revealed significant clumping of chromosomes in metaphase at all dose levels and the frequency of clumping increased as dosage increased. The euploidy number (2n = 40) of chromosomes per cell did not vary between the treatment groups and control groups. The frequency of nucleolus-organizing regions per cell did not change significantly between the treatment groups and the control. The frequency of sister chromatid exchanges increased significantly as the dosage increased.