Hematopoietic cancer

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

Pronounced increases were seen for total cancer, lymphatic and hematopoietic cancers, and leukemia in a mortality study of chlorohy-drin production workers." The investigators attributed the excesses to ethylene dichloride exposure based on probable exposures of the workers however, concomitant exposure to other chemicals precludes identifying the etiologic agent(s). 

Bone marrow Hematopoietic Cancer Immunodeficiencies Metabolic diseases Hemoglobinopathies Myocardial infarction... 

OH)2D3 inhibited proliferation and induced differentiation and apoptosis in human colon, breast, prostate and gynecological cancers as well as several forms of hematopoietic cancer (Studzinski and Moore, 1995 van Leeuwen and Pols, 1997). Experimental animal studies show that 1, 25(OH)2D3 inhibited chemically-induced breast, colon, and skin tumors. The growth of colon, breast and prostate cancer cells, as well as melanoma and retinoblastoma cells implanted into rodents was retarded by treatment with 1, 25(OH)2D3 (Studzinski and Moore, 1995 van den Bemd et al, 2000). 

Other studies also suggest increased risk of kidney, brain, bladder cancer, and soft-tissue sarcoma in addition to hematopoietic cancers after chronic-duration inhalation exposure to benzene (Greenland et al. 1994 Hunting et al. 1995 Lagorio et al. 1994b Serraino et al. 1992 Steineck et al. 1990). 

Secondary paraproteinemias may be seen in association with hematopoietic cancers (e.g., lymphomas and leukemias), other neoplasms (e.g., colon carcinoma), long-standing chronic urinary or biliary tract infection, rheumatoid factor related to IgM monoclonal protein, and amyloidosis. 

Lymphatic and hematopoietic cancer mortality only two deaths overall SMR value... 

Lymphatic and hematopoietic cancer mortality overall SMR value update of Brown and Jones (1981) study seven additional years follow-up... 

Hematologic cancer mortality (including lymphatic and hematopoietic cancers) Swedish capacitor manufacturing male workers employed 6 months versus Swedish national rates 142 1965-1982 1965-1978 (mean exposure 6.5 yrs) Observed versus expected 1 observed case The report identified one case of malignant lymphoma, expected number of cases was not reported, but the numbers of deaths from cancers was reported to correspond well with those expected. Median latency time=13 years. Gustavsson et al. 1986... 

Retroviruses hematopoietic cancers, sarcomas, carcinomas, leukemias Adult-T-cell leukemia... 

Concerning NO implication in hematopoietic cancer cells apoptosis, the situation is less clear. In U937 and HL60 cells, NO effects are very different although both cell lines have been established in culture from promyelocytic leukemia. NO-induced apoptosis in U937 cells (p53 negative cells) is a p53 and caspase independent pathway but is controlled by Bcl-2 [124]. In these cells NO inhibits caspase 3 by S-nitrosation... 

Gillespie WJ, Henry DA, O Connel DL, Kendrick S, JuszEZAK E, McInneny K and Derby L (1996) Development of hematopoietic cancers after implantation of total joint replacement. Clin Orthop 3295 290-296. 

El Daly H, Martens UM. Telomerase inhibition and telomere targeting in hematopoietic cancer cell lines with small non-nucleosidic synthetic compounds (BIBR1532). Methods Mol Biol 2007-, 405 47-60. 

The United States EPA has used several databases in their estimates for benzene exposure and risk. (Environmental Protection Agency, 5.0 Benzene, 5.1. Chemical and Physical Properties, EPA, 1988) The data utilized by flie EPA to assess the risk included the study by Rinsky et al. in 198U where the duration of exposure was at least 24 years and exposure levels are between 10 to 100 ppm (8 hour TWA) with a statistically significant increase incidence of leukemia. The study of Ott et al. in 1978 showed levels of anywhere from 2 to 25 ppm (8 hour TWA) with increased incidence of leukemia and Wong et al. 1983, where the exposure was at least 6 monflis, levels were from 1 ppm to 50 ppm, and there was a statistically significant increase in the incidence of leukemia, lymphatic and hematopoietic cancers. 

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