| Inorganic arsenic, given by injection to pregnant laboratory animals, can induce malformations. Arsenic methylation, which appears to be a detoxification step with respect to toxicity and teratogenicity, can be inhibited by periodate-oxidized adenosine (PAD). Diets deficient in protein provide a poor source of methyl donors and may result in impaired arsenic methylation. Thus this study sought to determine the effects of chemical inhibition of arsenic methylation and low intake of dietary protein on the developmental toxicity of inorganic arsenic.; Mated female CD-1 mice were given one of the following treatments on gestation day (GD) 9: Sodium arsenite, 7.5 mg/kg, ip, with 100 μM/kg PAD, ip, with a 5%, 10%, or 20% protein diet, or with a standard rodent diet; or sodium arsenate 17.9 mg/kg, ip, with 100 μM/kg PAD, ip, with a 5%, 10%, or 20% protein diet, or with a standard rodent diet. Control groups received a 5%, 10%, or 20% protein diet or the standard rodent diet. Test females were sacrificed on GD 18, and fetuses were examined for gross malformations and skeletal defects.; Pretreatment with PAD prior to either arsenical resulted in higher maternal toxicity and prenatal mortality and lower fetal weights. Significant increases in the incidence of exencephaly, ablepharia, and anomalies of the vertebral centra, sternebrae, and ribs were also caused by PAD pretreatment. Decreased dietary protein in the experimental groups treated with arsenic resulted in lower maternal weight gain, increased incidence of exencephaly, and skeletal defects such as malformations of the vertebral centra and sternebrae and the presence of fused ribs.; These results demonstrate that both the chemical methylation inhibitor PAD and dietary protein deficiency can enhance the developmental toxicity of inorganic arsenic. Human health effects from chronic arsenic exposure have been reported mainly in populations with low socioeconomic status and high levels of malnutrition. Individuals in such populations may have compromised arsenic methylating capacity and therefore may be more susceptible to arsenic-induced developmental toxicity. |
