Lymphocyte proliferation kinetics and genotoxic findings in a pilot study on individuals chronically exposed to arsenic in Mexico

Ostrosky‐Wegman, Patricia; Gonsebatt, María E.; Montero, Regina; Vega, Libia; Barba, H.; Espinosa, José; Palao, A.; C, Cortinas de Nava; Garcı́a-Vargas, Gonzalo G.; Razo, Luz M. Del; Cebrián, Mariano E.

doi:10.1016/0027-5107(91)90204-2

Cited by 120 publications

(52 citation statements)

References 24 publications

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“…Our data are consistent with the earlier reports that showed elevated incidence of CAs after chronic arsenic exposure. 10,11,50,51 Comparison of arsenic content in biological samples, frequencies of MN and CA with arsenic content in water…”

Section: Ca In Lymphocytesmentioning

confidence: 99%

“…8 Genotoxic effects of arsenic have been implicated in the carcinogenic outcomes. 9 Higher incidences of micronuclei (MN), chromosomal aberrations (CA), sister chromatid exchanges (SCE) and aneuploidy have been reported from the human populations exposed to arsenic through drinking water in various countries, such as Mexico, 10 Finland, 11 Argentina 12 and Taiwan. 8 The exact mechanism of arsenic-induced carcinogenicity is not yet fully understood, since it does not by itself induce cancer in animal models.…”

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confidence: 99%

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Cytogenetic damage and genetic variants in the individuals susceptible to arsenic‐induced cancer through drinking water

Ghosh

Basu

Mahata

et al. 2006

Intl Journal of Cancer

112

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In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenicinduced genotoxicity. ' 2005 Wiley-Liss, Inc.

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Section: Ca In Lymphocytesmentioning

confidence: 99%

mentioning

confidence: 99%

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic‐induced cancer through drinking water

Ghosh

Basu

Mahata

et al. 2006

Intl Journal of Cancer

112

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“…Thymocytes were incubated with or without 100 M of NaAsO 2 for 1 h at 37°C. In some groups, herbimycin A (HA, 10 g/ml) was added 4 h before the addition of NaAsO 2 , or staurosporine (STS, 10 g/ml) was added 5 min before the addition of NaAsO 2 kinases and c-Jun and for PARP degradation (Fig. 10).…”

Section: Cell Surface Chemical Event For Naaso 2 -Induced Intracellulmentioning

confidence: 99%

“…An alarming number of toxicity cases have been reported in these areas (1), in which arsenic has been found to cause immunotoxicity, immunosuppression, skin lesions, and increased risk of cancer (2)(3)(4)(5)(6). At the same time, renewed attention has been created due to the therapeutic application of arsenic in the treatment of lymphoid and hemopoietic neoplasmas such as acute promyelocytic leukemia (7).…”

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confidence: 99%

Arsenite Induces Apoptosis of Murine T Lymphocytes Through Membrane Raft-Linked Signaling for Activation of c-Jun Amino-Terminal Kinase

Hossain

Akhand

Kato

et al. 2000

The Journal of Immunology

111

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Because of its dual roles in acute toxicity and in therapeutic application in cancer treatment, arsenic has recently attracted a renewed attention. In this study, we report NaAsO2-induced signal cascades from the cell surface to the nucleus of murine thymic T lymphocytes that involve membrane rafts as an initial signal transducer. NaAsO2 induced apoptosis through fragmentation of DNA, activation of caspase, and reciprocal regulation of Bcl-2/Bax with the concomitant reduction of membrane potential. We demonstrated that NaAsO2-induced caspase activation is dependent on curcumin-sensitive c-Jun amino-terminal kinase and barely dependent on SB203580-sensitive p38 kinase or PD98059-sensitive extracellular signal-regulated kinase. Additionally, staurosporine, which severely inhibited the activation of mitogen-activated protein (MAP) family kinases and c-Jun, partially blocked the NaAsO2-mediated signal for poly(ADP-ribose) polymerase (PARP) degradation. Potentially as the initial cell surface event for intracellular signaling, NaAsO2 induced aggregation of GPI-anchored protein Thy-1 and superoxide production. This Thy-1 aggregation and subsequent activation of MAP family kinase and c-Jun and the degradation of PARP induced by NaAsO2 were all inhibited by DTT, suggesting the requirement of interaction between arsenic and protein sulfhydryl groups for those effects. β cyclodextrin, which sequestrates cholesterol from the membrane rafts, inhibited NaAsO2-induced activation of protein tyrosine kinases and MAP family kinases, degradation of PARP, and production of superoxide. In addition, β cyclodextrin dispersed NaAsO2-induced Thy-1 clustering. These results suggest that a membrane raft integrity-dependent cell surface event is a prerequisite for NaAsO2-induced protein tyrosine kinase/c-Jun amino-terminal kinase activation, superoxide production, and downstream caspase activation.

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“…While parasitic infections impair lymphocyte proliferation, MTZ treatment enhanced it. Chronic exposure to arsenic via drinking water inhibited lymphocyte stimulation and proliferation (27,28), especially in those individuals showing arsenic skin lesions; squamous cell carcinoma is one type of skin cancer frequently observed in these individuals and is the only type of cancer with a nonviral origin that is associated with immunosupression (29). Although these indexes are not specific parameters of immune impairment, they have been shown to be sensitive parameters in our human monitoring studies as a first approach to evaluate immunotoxic effects ( cEnhancement.…”

Section: Lymphocyte Proliferation Studiesmentioning

confidence: 99%

Environmental toxicants in developing countries.

Ostrosky‐Wegman

Gonsebatt

1996

Environ Health Perspect

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Health effects from environmental toxicants may be a more serious problem in developing countries compared with developed countries because the problem is potentiated by other factors: a) the lack of or failure to enforce regulations, which allows human exposures to genotoxic agents; b) undernourishment of the lower economic and social classes that comprise the most exposed populations from industrial and agricultural activities; and c) parasitic infections that afflict a wide range of populations in both urban and rural areas. Data on the genotoxic effects of different types of exposures, including environmental exposures (natural and industrial), occupational exposures, and infections and medical treatments, are presented and discussed with the point of view that all these factors must be taken into account with respect to regulation and the protection of human health. Occupational exposures in developing countries are higher than in developed countries due to lack of stringent regulations, lack of knowledge of the risks involved, and the negligence of workers. General pollution is another important issue since developed countries have established strict regulations and risky industrial processes are being exported to developing countries, along with banned substances and dangerous industrial wastes. It should be emphasized that stringent regulations in developed countries will not prevent exposures in the long term because toxic substances that are released into the environment will ultimately reach all our future generations. -Environ Health Perspect 1 04(Suppl 3): 599-602 (1996)

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Lymphocyte proliferation kinetics and genotoxic findings in a pilot study on individuals chronically exposed to arsenic in Mexico

Cited by 120 publications

References 24 publications

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic‐induced cancer through drinking water

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic‐induced cancer through drinking water

Arsenite Induces Apoptosis of Murine T Lymphocytes Through Membrane Raft-Linked Signaling for Activation of c-Jun Amino-Terminal Kinase

Environmental toxicants in developing countries.

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