Promotion of Rat Hepatocarcinogenesis by Dimethylarsinic Acid: Association with Elevated Ornithine Decarboxylase Activity and Formation of 8‐Hydroxydeoxyguanosine in the Liver

Wanibuchi, Hideki; Hori, Takaaki; Vijayaraghavan, Meenakshi; Ichihara, Toshio; Yamamoto, Shinji; Yano, Yoshihisa; Otani, Shuzo; Nakae, Dai; Konishi, Yoichi; Fukushima, Shoji

doi:10.1111/j.1349-7006.1997.tb00343.x

Cited by 72 publications

(36 citation statements)

References 27 publications

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“…Previous studies have reported an increase in levels of 8-OHdG in urine samples from mice gavaged with 720 mg/kg of DMA (Yamanaka et al, 2001). In a long-term study of carcinogenesis in rats, hepatic 8-OHdG levels were increased in DMA-treated rats, suggesting an increased effect of ROS on DNA (Wanibuchi et al, 1997).…”

Section: Introductionmentioning

confidence: 86%

Chronic arsenic exposure and urinary 8-Hydroxy-2′-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China

Fujino

Guo²,

Li³

et al. 2004

J Expo Sci Environ Epidemiol

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Objective: Recent studies have shown that generation of reactive oxidants during arsenic metabolism can play an important role in arsenic-induced injury. The purpose of this study was to examine the relationship between arsenic in drinking water and oxidative stress in humans by measuring 8-Hydroxy-2 0 -deoxyguanosine (8-OHdG). Methods: We performed a cross-sectional study in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 of the 143 inhabitants (93.7%) of the village participated in the study. The levels of 8-OHdG, arsenic and its metabolites were measured in urine collected from the participants. Regression analyses were performed to investigate the relationship between arsenic species and 8-OHdG levels in urine. Results: In the polluted village, monomethylarsenic was significantly higher in subjects with arsenic dermatosis than those without dermatosis despite no difference in mean levels of arsenic in well water between both types of subject. For subjects with arsenic dermatosis, arsenic species and metabolites in urine are significantly associated with 8-OHdG, while there was no statistically significant relationship for subjects without arsenic dermatosis. For all residents of the polluted village, the levels of dimethylarsenic and 8-OHdG were significantly higher for those who had been exposed to well water for more than 12 years. Conclusions: These results provide evidence of a link between exposure to arsenic from drinking water and oxidative stress, which may play an important role in arsenic-involved injuries.

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Section: Introductionmentioning

confidence: 86%

Chronic arsenic exposure and urinary 8-Hydroxy-2′-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China

Fujino

Guo²,

Li³

et al. 2004

J Expo Sci Environ Epidemiol

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“…DMeAs, a metabolite of iAs, induced DNA damage via formation of ·O 2 -and dimethylarsenic peroxyl radical (39,40). 8-Hydroxy-2´-deoxyguanosine (8-OhdG), one of the major ROS-induced DNA basemodified products, was detected in the skin of patients with arsenic-related Bowen's disease (41) and in the liver of rats administered DMeAs (42). Our recent data (43) from animal experiments revealed that ·O 2 -, which was identified as a Tiron-reactive signal (Dojindo Lab., Kumamoto, Japan), was generated in intact aortic rings from rabbits chronically exposed to 5 mg/L of arsenate in drinking water for 18 weeks.…”

Section: Discussionmentioning

confidence: 99%

Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water.

Yamauchi

Kumagai

et al. 2002

Environ Health Perspect

246

140

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Exposure of experimental animals or cultured cells to arsenic induces oxidative stress, but, to date, no examination of this phenomenon in humans has been reported. In this study we conducted a cross-sectional study in Wuyuan, Inner Mongolia, China, to explore the relationship between chronic arsenic exposure from drinking water and oxidative stress in humans. Thirty-three inhabitants who had been drinking tube-well water with high concentrations of inorganic arsenic (mean value = 0.41 mg/L) for about 18 years constituted the high-exposure group, and 10 residents who lived nearby but were exposed to much lower concentrations of arsenic in their drinking water (mean value = 0.02 mg/L) were selected as the low-exposure comparison group. Results of the present study indicated that although the activity for superoxide dismutase (SOD) in blood did not differ significantly between the two groups, the mean serum level of lipid peroxides (LPO) was significantly higher among the high-exposed compared with the low-exposed group. Elevated serum LPO concentrations were correlated with blood levels of inorganic arsenic and its methylated metabolites. In addition, they showed an inverse correlation with nonprotein sulfhydryl (NPSH) levels in whole blood. The subjects in the high-arsenic-exposure group had mean blood NPSH levels 57.6% lower than those in the low-exposure group. Blood NPSH levels were inversely correlated with the concentrations of inorganic arsenic and its methylated metabolites in blood and with the ratio of monomethylarsenic to inorganic arsenic. These results provide evidence that chronic exposure to arsenic from drinking water in humans results in induction of oxidative stress, as indicated by the reduction in NPSH and the increase in LPO. Some possible mechanisms for the arsenic-induced oxidative stress are discussed.

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“…Directly or indirectly, arsenic-induced oxidative stress can induce further damages in cells, and these oxidative injuries are reported to associate with arsenical carcinogenesis. Both in mouse and human skins, arsenic can induce oxidative damage in cellular DNA and generate 8-hydroxyl-2¢-deoxylguanosine (8-OHdG) oxidative DNA adducts [24][25][26]. Clinical studies in arsenic-induced Bowen's disease (As-BD) indicate that the increased 8-OHdG levels are positively correlated to the lesional arsenic concentration [26], suggesting the involvement of oxidative stress in arsenical skin carcinogenesis.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

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SummaryChronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed skin. The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas. There was a decrease in the number of Langerhans cells in As-BD lesion which results in an impaired immune function on the lesional sites. Since CD4+ cells are the target cell affected by As, the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenic-induced skin cancer. In this

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Promotion of Rat Hepatocarcinogenesis by Dimethylarsinic Acid: Association with Elevated Ornithine Decarboxylase Activity and Formation of 8‐Hydroxydeoxyguanosine in the Liver

Cited by 72 publications

References 27 publications

Chronic arsenic exposure and urinary 8-Hydroxy-2′-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China

Chronic arsenic exposure and urinary 8-Hydroxy-2′-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China

Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water.

Arsenic Carcinogenesis in the Skin

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