Two of three studies that assessed risk by duration of employment as a welder showed positive trends.3,4 These studies also showed increased ocular melanoma risk associated with eye burns-a proxy for ...UV exposure-and one reported a positive exposure-response association for cumulative occupational exposure to artificial UV radiation, including welding.3,4 Risks persisted after adjustment for sun exposure, sun bed use, or both.4-6 Welding fumes are produced when metals heated above their melting point vaporise and condense to fine particles (mostly <1 μm in size). In one oropharyngeal aspiration study and one inhalation study in male A/J mice, gas metal arc-stainless steel welding fumes promoted 3-methylcholanthrene-induced lung tumours.13,14 Absorption and excretion of metals (chromium, nickel, and manganese) was shown in people exposed to welding fumes, but data for particle deposition and clearance in welders were scarce. 2 International Agency for Research on Cancer, Chromium, nickel and welding, IARC Monogr Eval Carcinog Risks Hum, Vol. 49, 1990, 1-648 3 CM Vajdic, A Kricker, M Giblin, Artificial ultraviolet radiation and ocular melanoma in Australia, Int J Cancer, Vol. 112, 2004, 896-900 4 P Guenel, L Laforest, D Cyr, Occupational risk factors, ultraviolet radiation, and ocular melanoma: a case-control study in France, Cancer Causes Control, Vol. 12, 2001, 451-459 5 EA Holly, DA Aston, DK Ahn, AH Smith, Intraocular melanoma linked to occupations and chemical exposures, Epidemiology, Vol. 7, 1996, 55-61 6 JM Seddon, ES Gragoudas, RJ Glynn, KM Egan, DM Albert, PH Blitzer, Host factors, UV radiation, and risk of uveal melanoma. A case-control...
Objective: We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data Sources: We assessed data from relevant epidemiologic studies concerning environmental ...inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis: Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose-response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion: Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important.
DCM was classified as probably carcinogenic to humans (Group 2A) on the basis of limited evidence that it causes biliary-tract cancer and non-Hodgkin lymphoma in humans and sufficient evidence of ...carcinogenicity in experimental animals (malignant lung and hepatocellular tumours in male and female mice).2,3,6-9 In making its overall assessment, the working group also took into account the strong evidence that DCM metabolism via glutathione-S-transferase T1 (GSTT1) leads to the formation of reactive metabolites, that GSTT1 activity is strongly associated with genotoxicity of DCM in vitro and in vivo, and that GSTT1-mediated metabolism of DCM does occur in humans. DNA reactivity was evident in various genotoxicity assays, including in animals and in human cells in vitro. Because 1,3-PS does not require metabolic activation and reacts directly with DNA and other macromolecules, the working group concluded that this mechanism probably operates both in animals and humans.
In gavage studies, tetrabromobisphenol A caused an increase in the incidence of hepatoblastoma, hepatocellular carcinoma or hepatoblastoma (combined), haemangiosarcoma, and large intestine tumours in ...male mice, and induced uterine adenocarcinomas and rare malignant mixed Müllerian uterine tumours in female rats.12 Tetrabromobisphenol A interacts with human nuclear receptors, including thyroid-hormone receptor and PPAR-γ.13 It modulates enzymes relevant to the endocrine system, including aromatase, and is a potent inhibitor of oestrogen sulfotransferase.14,15 Tetrabromobisphenol A induces oxidative stress in human cells in vitro and in multiple species in vivo, and has immunosuppressive effects in human natural killer cells in vitro and in mice in vivo.16 A majority of Working Group members supported a group 2A classification based on "sufficient evidence of carcinogenicity in experimental animals", and strong mechanistic evidence. Pentachlorophenol and some related compounds Monograph Working Group Members C W Jameson (USA; Meeting Chair); I Linhart (Czech Republic); H U Käfferlein (Germany); G Ichihara (Japan); T Nomiyama (Japan); K Ogawa (Japan); H Kromhout (Netherlands); M van den Berg (Netherlands); M M Marques (Portugal); M A Abdallah (UK); R C Cattley (USA); A Ducatman (USA); J K Dunnick (USA); K W Hanley (USA); K Houck (USA); R Melnick (USA); F E Mirer (USA); S Nesnow (USA); A M Ruder (USA); J M Sanders (USA); K Steenland (USA); R T Zoeller (USA) Declaration of interests RM was involved in litigation on bladder cancer and exposure to p-cresidine and D-toluidine; KO is an employee of the Japanese Government; all other Working Group Members declare no competing interests Invited specialists D C Glass (Australia); T Sorahan (UK) Declaration of interests DCG has received funding from the Australian Institute of Petroleum; TS has received research awards from the rubber industry and the petroleum industry Representatives M Bisson (National Competence Centre for Industrial Safety and Environmental Protection; France) Declaration of interests All representatives declare no competing interests Observers S Borghoff (American Chemistry Council's North American Flame Retardant Alliance; USA); W Dekant (Bromine Science and Environmental Forum; Belgium); P Erkekoglu (Hacettepe University; Turkey); S Jacobi (Albemarle Europe SPRL; Belgium); O Manor (ICL-Industrial Products; Israel); V Thomas (University Paris Dauphine; France) Declaration of interests SB has provided research and consulting services for the North American Flame Retardant Alliance panel of the American Chemistry Council; WD has received financial support from the Bromine Science and Environmental Forum for a report on tetrabromobisphenol A and from the American Chemistry Council.
Abstract Our prior work showed that brief exposure of pregnant C3H mice to inorganic arsenic-induced hepatocellular carcinoma (HCC) formation in adult male offspring. The current study examined the ...early hepatic events associated with this oncogenic transformation. Pregnant mice were exposed to a known carcinogenic dose of arsenic (85 ppm) in the drinking water from gestation days 8 to 18. The dams were allowed to give birth and liver samples from newborn males were analyzed for arsenic content, global DNA methylation and aberrant expression of genes relevant to the carcinogenic process. Arsenic content in newborn liver reached 57 ng/g wet weight, indicating arsenic had crossed the placenta, reached the fetal liver and that significant amounts remained after birth. Global methylation status of hepatic DNA was not altered by arsenic in the newborn. However, a significant reduction in methylation occurred globally in GC-rich regions. Microarray and real-time RT-PCR analysis showed that arsenic exposure enhanced expression of genes encoding for glutathione production and caused aberrant expression of genes related to insulin growth factor signaling pathways and cytochrome P450 enzymes. Other expression alterations observed in the arsenic-treated male mouse newborn liver included the overexpression of cdk-inhibitors and stress response genes including increased expression of metallothionein-1 and decreased expression of betaine-homocysteine methyltransferase and thioether S -methyltransferase. Thus, transplacental exposure to arsenic at a hepatocarcinogenic dose induces alterations in DNA methylation and a complex set of aberrant gene expressions in the newborn liver, a target of arsenic carcinogenesis.
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