Effects of protein deficient diets on the developmental toxicity of inorganic arsenic in mice.
BACKGROUND
Inorganic arsenic, when given by injection to pregnant laboratory animals (mice, rats, hamsters), has been shown to induce malformations. Arsenic methylation may be a detoxification step, and diets deficient in protein are a poor source of methyl donors and may possibly result in impaired arsenic methylation. Human health effects from chronic arsenic exposure have been reported mainly in populations with low socioeconomic status. Individuals in such populations are likely to suffer from malnutrition, which can compromise embryonic/fetal development and diminish arsenic methylating capacity. We sought to determine if dietary protein deficiency affects the developmental toxicity of inorganic arsenic.


METHODS
Mated females were randomly assigned to one of 12 treatment groups. Experimental groups received either AsIII or AsV i.p. on Gestation Day 8 (GD 8, plug=GD 0) and were maintained on a 5%, 10%, or 20% protein custom mixed diet from GD 1 until sacrifice. Controls received the custom diets alone, were given AsIII or AsV i.p. on GD 8 with Teklad LM-485 rodent diet, or were fed the LM-485 diet alone. Test females were sacrificed on GD 17, and their litters were examined for mortality and developmental defects.


RESULTS
Arsenic plus dietary protein deficiency decreased maternal weight gain and increased the incidences of exencephaly, ablepharia, and skeletal defects, such as malformed vertebral centra, fused ribs, and abnormal sternebrae (bipartite, rudimentary, or unossified).


CONCLUSIONS
These results demonstrate that dietary protein deficiency enhances the developmental toxicity of inorganic arsenic, possibly by impairment of arsenic methylation.
Lammon
Carol A
CA
Capstone College of Nursing, The University of Alabama, Tuscaloosa, Alabama, USA.
Hood
Ronald D
RD
D000014:Abnormalities, Drug-Induced; D000821:Animal Feed; D000818:Animals; D001151:Arsenic / Q000009:adverse effects / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004044:Dietary Proteins / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D018811:Maternal Exposure; D008745:Methylation; D051379:Mice; D009752:Nutritional Status; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D011488:Protein Deficiency; D011897:Random Allocation; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D004044:Dietary Proteins; D013723:Teratogens; D001151:Arsenic