Gene Expression Analysis of Pre- and Peri-Natal Fetal Rat Liver Exposed to Arsenic

It is a well-known fact that arsenic poisoning by way of ingestion may lead to death and has been used to commit various murders over the years. Through research arsenic has become a known human carcinogen. Various disorders such as black-foot disease, skin lesions, genetic mutations and cancers of the bladder, skin, kidney, lung, nasal passage, prostate and liver have all been linked to arsenic exposure. The leading cause of accidental poisoning of arsenic is through the ingestion of ground water that naturally contains high concentrations of arsenic. During gestation, research shows that arsenic can easily transfer across the placenta to the fetus in both humans and rodents. Furthermore, studies have revealed that small amounts of arsenic can also be passed to infants through the breast milk. Arsenic has characteristics that are known to cause cancer· through deregulation of known genes, such as the target genes analyzed in this study Cyclin Dl, manganese superoxide dismutase (MnSOD), and proliferating cell 1 2 nuclear antigen (PCNA). Little research has been done thus far exploring the effects of arsenic on the liver of fetal rats specifically. The postulation of this study is that the fetal rat liver during pre-natal and peri-natal exposure exposure to arsenic will show changes - in gene expression in genes associated with cancer. To test this hypothesis, timed pregnant Harlan \u27Sprague Dawley (HSD) rats consumed arsenic tainted water during gestation, and this experimental group was sacrificed and the tissues harvested, while the second experimental group was allowed to breast feed until ten days after birth before sacrifice. The animals exposed during gestation are referred to as the pre-natal group and the group exposed through gestation and breast feeding are referred to as the perinatal group. After harvesting the livers of the pups, RNA was isolated, cDNA was prepared from that RNA, and Real Time Polymerase Chain Reaction was performed using primers for genes involved in cell proliferation: Cyclin Dl, PCNA, and MnSOD. Of the genes studied, Cyclin Dl, PCNA, and MnSOD showed upregulation in the perinatal group. In the prenatal group, Cyclin Dl, PCNA, and MnSOD showed downregulation, suggesting that cell proliferation in the fetuses was affected differently by arsenic exposure through the placenta. This observation may be explained by the characteristics of the liver in conjunction with the placenta. The placenta metabolizes xenobiotic molecules and may prevent these molecules from affecting the developing fetus. This study confirmed that the exposure to arsenic effects the expression of cell proliferating genes in the liver, and has divergent effects on the prenatal and perinatal groups