Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China

Lin, Gang; Du, Hui; Chen, Jigang; Lu, Hongchao; Kai, Jin-xiang; Zhou, Yuhang; Guo, Weibo; Zhang, Xinjiang; Lu, Daru; Golka, Klaus; Shen, Jianhua

doi:10.1007/s00204-007-0187-4

Cited by 30 publications

(12 citation statements)

References 14 publications

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“…A similar observation was reported by Wang et al [12], in which there are interindividual differences in excretion profiles and the relative concentrations of major arsenic species in urine among four Chinese APL patients undergoing ATO treatment. It is significant to note that genetic polymorphisms in arsenic metabolism genes, such as human arsenic methyltransferase (AS3MT) gene and glutathione S-transferase gene, are considered to be related to interindividual variation in the arsenic metabolism [31-33]. Collectively, continuous efforts to understand the differences in arsenic metabolism and the relationship between these genetic polymorphisms and arsenic metabolism among patients are definitely useful for providing an effective treatment protocol of ATO for individual APL patients, ultimately contribute to reduction of its side effects.…”

Section: Discussionmentioning

confidence: 99%

Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

et al. 2012

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BackgroundSpeciation of arsenic trioxide (ATO) metabolites in clinical samples such as peripheral blood (PB) from acute promyelocytic leukemia (APL) patients has been conducted. However, speciation of arsenicals in bone marrow (BM) has not yet been performed. Profiles of arsenic speciation in plasma of BM were thus investigated and compared with those of PB plasma from a relapsed APL patient. The total arsenic concentrations in high molecular weight fraction (HMW-F) of BM and PB plasma were also determined.MethodsResponse assessment was evaluated by BM aspirate examination and fluorescence in situ hybridization analysis. The analyses of total arsenic concentrations and speciation were preformed by inductively coupled plasma mass spectrometry (ICP-MS), and high-performance liquid chromatography (HPLC)/ICP-MS, respectively.ResultsResponse assessment showed that the patient achieved complete remission. The total arsenic concentrations in BM plasma increased with time during the consecutive administration. The PB plasma concentrations of methylated arsenic metabolites substantially increased after the start of administration, while those of inorganic arsenic were still kept at a low level, followed by substantially increase from day-14 after administration. The arsenic speciation profiles of PB plasma were very similar to those of BM plasma. Furthermore, the total arsenic concentrations of HMW-F in BM plasma were much higher than those in PB plasma.ConclusionsThe behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the attack of free arsenic species.

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Section: Discussionmentioning

confidence: 99%

Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

et al. 2012

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“…Of these proposed key events, experimental evidence suggests sustained oxidative stress production may play an especially important role in As‐mediated carcinogenesis in the skin [reviewed in [65]]. Mutations in oxidative stress response genes are positively correlated with As‐mediated skin disease development in chronically exposed populations [66–69], and ROS‐associated DNA lesions [i.e., 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG)] are significantly associated with As‐related human skin tumors [70, 71]. The global gene transcription profiles of human hyperkeratoses (HKs), which are benign, potentially premalignant lesions associated with chronic iAs exposure [72, 73], reveal that the vast majority of most significantly altered functions (apoptosis, cell‐cycle regulation, proliferation, cellular differentiation) and pathways (e.g., MAPKs, Wnt/β‐catenin, calcium signaling, NF‐κB) in HKs compared to normal skin can be altered by oxidative stress [74–77].…”

Section: Discussionmentioning

confidence: 99%

Gene expression of normal human epidermal keratinocytes modulated by trivalent arsenicals

Bailey

Hester

Knapp

et al. 2010

Molecular Carcinogenesis

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Chronic exposure to inorganic arsenic (iAs) is associated with the development of benign and malignant human skin lesions including nonmelanoma skin cancers. The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (iAs(III)) and two of its toxic metabolites, monomethylarsonous acid (MMA(III)) and methylarsinous acid (DMA(III)), are attractive candidates. In an effort to better understand and compare their toxic effects in the skin, we compared the global gene expression profiles of normal human epidermal keratinocytes (NHEKs) exposed to varying noncytotoxic/slightly cytotoxic concentrations of iAs(III), MMA(III), and DMA(III) for 24 h. Exposure to each arsenical treatment group exhibited a dose effect in the number of altered genes and the magnitude of expression change in NHEKs. The most significant gene expression changes associated with iAs(III) and MMA(III) exposure were consistent with several key events believed to be important to As-driven skin carcinogenesis, namely induction of oxidative stress, increased transcript levels of keratinocyte growth factors, and modulation of MAPK and NF-κB pathways. At both comparable arsenical concentrations and comparable NHEK toxicity, greater potential carcinogenic effects were observed in MMA(III)-exposed NHEKs than those exposed to iAs(III), including involvement of more proinflammatory signals and increased transcript levels of more growth factor genes. In contrast, none of these above-mentioned transcriptional trends were among the most significantly altered functions in the DMA(III) treatment group. This study suggests the relative capacity of each of the tested arsenicals to drive suspected key events in As-mediated skin carcinogenesis is MMA(III) > iAs(III) with little contribution from DMA(III).

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“…For decades, the total As concentration in the drinking water sources in this village has never been detected to exceed the level the Chinese National Criteria requires (\0.05 mg/l; Liu et al 2002;An et al 2007;Lin et al 2006Lin et al , 2007. Water samples collected from all 4 drinking water sources in this village during this study showed As concentrations within the range of 0.014-0.025 mg/l (0.0181 ± 0.0049 mg/l; Lin et al 2006).…”

Section: Discussionmentioning

confidence: 98%

Factors impacting on the excess arseniasis prevalence due to indoor combustion of high arsenic coal in a hyperendemic village

Lin

Meng

et al. 2009

Int Arch Occup Environ Health

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Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China

Cited by 30 publications

References 14 publications

Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

Gene expression of normal human epidermal keratinocytes modulated by trivalent arsenicals

Factors impacting on the excess arseniasis prevalence due to indoor combustion of high arsenic coal in a hyperendemic village

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