Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

Abstract

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

“…Human genome-wide association studies for mutations promoting arsenic susceptibility identified an AS3MT haplotype that leads to reduced expression of AS3MT and increased toxicity ( Das et al, 2016 ). Recently it was shown that C57BL/6J mice are more susceptible to arsenic-induced oxidative liver injury than 129X1/SvJ mice, and that this difference is related to their reduced capacity for arsenic methylation ( Wu et al, 2017 ). In addition, one study found that alcohol use may decrease methylation of iAs ( Hopenhayn-Rich et al, 1996 ; Tseng, 2009 ).…”

MicroRNA‐210 Promotes Bile Acid–Induced Cholestatic Liver Injury by Targeting Mixed‐Lineage Leukemia‐4 Methyltransferase in Mice

“…D) is consistent with decreased Shp expression in cholestatic C57BL/6 mice induced by BDL but inconsistent with increased Shp expression in 129x1/SvJ mice fed CA‐chow for 1 week . The 129x1/SvJ mice have a profound defect in response to inflammatory stimulus, and C57BL/6 mice are more susceptible to liver damage than 129x1/SvJ mice, so the differences in hepatic responses to BA‐induced toxicity, including Shp expression, are likely a strain‐specific effect.…”

Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations

“…Although the function of KLHDC4 remains largely elusive, our results revealed that decreased Klhdc4 expression triggers the Atf4 pathway, leading to dysregulation of genes in both apoptosis and adaptive responses to stress. In fact, relative to 129S1/SvJ, C57BL/6J mice were reported to be more susceptible to oxidative hepatic injury after acute arsenic exposure 71 , indicating different stress responses among mouse strains. It is worth noting that increased translation of Atf4 mRNA is stimulated by phosphorylation of several eIF2 kinases in response to different cellular stresses.…”