The Distribution in Tissues and Urine of Arsenic Metabolites After Subchronic Exposure to Dimethylarsinic Acid (DMAV) in Rats

Abstract

Dimethylarsinic acid (DMA(V)) acted as cancer promoter promoted urinary bladder, liver, and lung carcinogenesis in rats. Understanding of the distribution of arsenicals in critical sites will aid to define the action of DMA(V)-induced toxicity and carcinogenicity. The present experiment was conducted to compare the accumulated levels of arsenicals in the liver, kidney, and bladder of both male and female rats after subchronic exposure to DMA(V). After exposure to DMA(V) in drinking water for 10 weeks, urinary DMA concentrations of 100 and 200 ppm DMA(V)-treated rats increased significantly compared with those of the control rats. Smaller amount of trimethylarsinic acid (TMA) was detected in urine, but not in liver, kidney, and bladder muscle. In the liver and kidney, the levels of DMA in DMA(V)-treated rats significantly increased compared with those of the control group, but there was no difference between 100 and 200 ppm DMA(V)-treated rats. DMA did not accumulate in bladder muscle. There was no difference for DMA concentrations between male and female rats. Our results suggest that the accumulation of DMA in the liver and kidney was saturated above 100 ppm DMA(V) treatment concentration, and DMA(V) was a little partly metabolized to TMA, and TMA was rapidly excreted into urine.

All‐Trans Retinoic Acid Ameliorates Arsenic‐Induced Oxidative Stress and Apoptosis in the Rat Uterus by Modulating MAPK Signaling Proteins

“…Arsenite is methylated first to monomethylarsonic acid (MMA) and subsequently to dimethylarsinic acid (DMA) and in some species to trimethylarsine oxide (TMAO). However, in rodents, DMA was found to be readily methylated to TMAO [Vahter, 1999;N emeti and Gregus, 2013;Liu et al, 2015], thereby the probable cause of toxicity observed in our results. In most mammals, DMA is the end point of arsenic metabolism and is rarely further methylated [Yamauchi and Yamamura, 1985;Yoshida et al, 1988].…”

“…In most mammals, DMA is the end point of arsenic metabolism and is rarely further methylated [Yamauchi and Yamamura, ; Yoshida et al, ]. However, in rodents, DMA was found to be readily methylated to TMAO [Vahter, ; Németi and Gregus, ; Liu et al, ], thereby the probable cause of toxicity observed in our results. Recently, however, it has been proposed that DMA (V) is the predominant metabolite in rat plasma as well [Chen et al, ].…”

Distinct Metabolic Signature of Human Bladder Cancer Cells Carrying an Impaired Fanconi Anemia Tumor-Suppressor Signaling Pathway

“…14 Currently, metabolomics has demonstrated its practicality by the identification of BC biomarkers in urine, 15,16 plasma and tissue samples. 17,18 Additionally, metabolic studies in cell culture are highly valuable 19 as they can identify functional biomarkers that represent cellular processes, 20,21 and/or provide insights into the individuality of various cancer cell lines. 22,23 These are essential for a comprehensive understanding of cancer cell biology and to complement clinical studies.…”

Arsenic Metabolites and Methylation Capacity Among Individuals Living in a Rural Area with Endemic Arseniasis in Inner Mongolia, China

“…Even moderately elevated concentrations of inorganic arsenic (iAs) in drinking water pose a serious public health problem [2]. Previous epidemiological studies of individuals exposed to high arsenic levels in drinking water suggest that chronic arsenic exposure via drinking water is widely associated with a higher risk of skin lesions, hypertension, diabetes, cardiovascular diseases, and cancer of the skin, lungs, bladder, liver, and possibly kidneys [2][3][4][5][6][7][8][9][10][11][12]. Therefore, the World Health Organization guideline for arsenic in drinking water is 10 μg/L [13].…”