Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study.

Introduction: High-throughput loss-of-function genetic screening tools in yeast or other model systems except in mammalian cells have been implemented to study human susceptibility to chemical toxicity. Here, we employed a newly developed human haploid cell (KBM7)-based mutagenic screening model (KBM7-mu cells) and examined its applicability in identifying genes whose absence allows cells to survive and proliferate in the presence of chemicals.

Methods: KBM7-mu cells were exposed to 200 μM Chlorpyrifos (CPF), a widely used organophosphate pesticide, a dose causing approximately 50% death of cells after 48h of treatment.

Chronic low level trimethyltin exposure and the risk of developing nephrolithiasis.

Objectives: Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H(+)/K(+) ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis.

Toxicity of trimethyltin and dimethyltin in rats and mice.

Extensive uses of methyltin compounds in polyvinyl chloride (PVC) production have led to a dramatic increase of occupational-related methyltin poisoning accidents and the widespread contamination of methyltins in various environmental media. Here, we conducted studies to compare the acute toxicity induced by trimethyltin (TMT) and dimethyltin (DMT), and investigated the cumulative toxic effects of TMT in rats and mice. Neurobehavioral changes were observed in rats and mice treated with either DMT or TMT, but we also observed that both TMT and DMT exposure in rats significantly lowered the blood potassium level.