Lack of Promoting Potential of Dimethylarsinic Acid in the Kidney of Male NCI-Black Reiter Rats.

Vijayaraghavan, Meenakshi; Wanibuchi, Hideki; Yamamoto, Shinji; Hakoi, Kazuo; Nakae, Dai; Konishi, Yoichi; Fukushima, Shoji

doi:10.1293/tox.13.87

Cited by 3 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Klaunig et al 27. proposed that oxidative stress can play important roles in “nongenotoxic” hepatic carcinogenesis, and in previous studies from our laboratory, we obtained evidence that the active metabolite of DMA causes DNA damage via oxygen radicals 11, 28, 29. The present study shows that methylated arsenicals form oxygen radicals and generate 8‐OHdG.…”

Section: Discussionsupporting

confidence: 74%

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S‐transferase placental form positive foci: A possible reactive oxygen species mechanism

Nishikawa

Wanibuchi

Ogawa

et al. 2002

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO)] on rat liver carcinogenesis using a liver medium-term bioassay (the Ito test). Male, 10-week-old, F344 rats were given a single i.p. injection of diethylnitrosamine at a dose of 200 mg/kg b.w. as an initiator. Starting 2 weeks thereafter they received 100 ppm of MMA, DMA or TMAO in their drinking water, or no supplement as a control, for 6 weeks. All animals underwent 2/3 partial hepatectomy in week 3 after initiation. Quantification of glutathione S-transferase placental form (GST-P)-positive foci as preneoplastic lesions in liver sections revealed significantly increased numbers and areas in all 3 treated groups compared with controls. Hepatic microsome cytochrome P-450 content was markedly increased with all 3 arsenic treatments. Markedly elevated CYP 2B1 protein levels and CYP 2B1/2 mRNA levels were thus observed in all cases. The potency of promotion was similar for MMA, DMA and TMAO. Since hydroxyradicals were found to be generated in the relatively early phase while methylated arsenicals were metabolized in liver, the resultant oxidative stress might have promoted lesion development. © 2002 Wiley-Liss, Inc. Key words: arsenic; hepatocarcinogenesis enhancement; oxidative stress; cytochrome P-450Drinking water contamination by arsenicals remains a major public health problem in many parts of the world. Epidemiologic research on arsenic has demonstrated significantly higher standardized mortality rate for cancers of the kidney, liver and colon, with especially high rates in the skin, urinary bladder and lung. 1,2 For causal factors in arsenic epidemiology, the focus has been on inorganic arsenite (AsIII) and arsenate (AsV), but experimental evidence was limited until recently. 3 Methylation of inorganic arsenics has been considered to result in detoxication. Thus inorganic arsenicals are methylated into dimethylarsinic acid (DMA), which is then excreted from the human body via the urine. 4 However, DMA may induce mitotic arrest in V79 cells, with potent clastogenic effects in human fibroblast cells and DMA has caused aneuploidy in mouse bone marrow cells. [5][6][7] Recent research demonstrated a promotion potential for DMA in the urinary bladder, kidney, liver and thyroid gland using a multiorgan carcinogenesis bioassay in rats, and also for skin tumorigenesis in mice. 8,9 We have also established that DMA promotes urinary bladder and liver carcinogenesis in a dose-dependent manner. 10,11 Moreover, DMA was found to be carcinogenic for the urinary bladder on long-term exposure to rats. 12 Monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) are also related methylated metabolites of inorganic arsenate and arsenite. [13][14][15] In the present study the 3 organic arsenics MMA...

show abstract

Section: Discussionsupporting

confidence: 74%

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S‐transferase placental form positive foci: A possible reactive oxygen species mechanism

Nishikawa

Wanibuchi

Ogawa

et al. 2002

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Vijayaraghavan et al. ( 2000 ) found that 200 mg/L DMA(V) in drinking water did not promote renal or liver carcinogenesis in rats pretreated with N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN).…”

Section: Assessmentmentioning

confidence: 99%

“…Chen et al (1999) reported that administration of DMA(V) in drinking water for 6 weeks to male rats increased the incidence of urinary bladder tumours induced by BBN. Vijayaraghavan et al (2000) found that 200 mg/L DMA(V) in drinking water did not promote renal or liver carcinogenesis in rats pretreated with N-ethyl-N-hydroxyethylnitrosamine (EHEN). Nishikawa et al (2002) pretreated groups of 20 rats with diethylnitrosamine (DEN) and then administered MMA(V), DMA(V) or TMAO at 100 mg/L (equivalent to 12 mg/kg bw per day MMA(V), DMA(V) or TMAO 33 ) or no arsenic compound, in drinking water, for 6 weeks.…”

Section: Cell Transformationmentioning

confidence: 99%

Risk assessment of small organoarsenic species in food

Schrenk,

Bignami,

Bodin

et al. 2024

EFS2

View full text Add to dashboard Cite

The European Commission asked EFSA for a risk assessment on small organoarsenic species in food. For monomethylarsonic acid MMA(V), decreased body weight resulting from diarrhoea in rats was identified as the critical endpoint and a BMDL10 of 18.2 mg MMA(V)/kg body weight (bw) per day (equivalent to 9.7 mg As/kg bw per day) was calculated as a reference point (RP). For dimethylarsinic acid DMA(V), increased incidence in urinary bladder tumours in rats was identified as the critical endpoint. A BMDL10 of 1.1 mg DMA(V)/kg bw per day (equivalent to 0.6 mg As/kg bw per day) was calculated as an RP. For other small organoarsenic species, the toxicological data are insufficient to identify critical effects and RPs, and they could not be included in the risk assessment. For both MMA(V) and DMA(V), the toxicological database is incomplete and a margin of exposure (MOE) approach was applied for risk characterisation. The highest chronic dietary exposure to DMA(V) was estimated in ‘Toddlers’, with rice and fish meat as the main contributors across population groups. For MMA(V), the highest chronic dietary exposures were estimated for high consumers of fish meat and processed/preserved fish in ‘Infants’ and ‘Elderly’ age class, respectively. For MMA(V), an MOE of ≥ 500 was identified not to raise a health concern. For MMA(V), all MOEs were well above 500 for average and high consumers and thus do not raise a health concern. For DMA(V), an MOE of 10,000 was identified as of low health concern as it is genotoxic and carcinogenic, although the mechanisms of genotoxicity and its role in carcinogenicity of DMA(V) are not fully elucidated. For DMA(V), MOEs were below 10,000 in many cases across dietary surveys and age groups, in particular for some 95th percentile exposures. The Panel considers that this would raise a health concern.

show abstract

Dimethylarsinic acid induces 8-hydroxy-2′-deoxyguanosine formation in the kidney of NCI-Black-Reiter rats

et al. 2001

View full text Add to dashboard Cite

Lack of Promoting Potential of Dimethylarsinic Acid in the Kidney of Male NCI-Black Reiter Rats.

Cited by 3 publications

References 40 publications

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S‐transferase placental form positive foci: A possible reactive oxygen species mechanism

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S‐transferase placental form positive foci: A possible reactive oxygen species mechanism

Risk assessment of small organoarsenic species in food

Dimethylarsinic acid induces 8-hydroxy-2′-deoxyguanosine formation in the kidney of NCI-Black-Reiter rats

Contact Info

Product

Resources

About