[Chromium gastrointestinal disease, a little known occupational disease induced by chromates].
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In June 1990, the Dallas (Texas) County Health Department received a physician's report of an elevated blood lead level (BLL) (52 micrograms/dL) for an employee of a company that formulates color concentrates for the plastics industry. The physician had been evaluating the employee for severe headaches of uncertain etiology; however, he requested a BLL analysis when the employee's occupational history suggested possible lead exposure.
The possible carcinogenicity of insoluble chromium (VI) compound, PbCrO4, in human cells has been tested using a nontumorigenic human osteosarcoma cell line (HOS, TE 85). Electron microscopic studies show that PbCrO4 is phagocytosed by HOS cells and accumulates within the vacuoles in the cytoplasm. A number of cell lines have been isolated following multiple treatment of HOS cells with PbCrO4. These cell lines are morphologically different from HOS cells, form anchorage-independent colonies in soft agar and form quickly regressing small tumor nodules in athymic nude mice. The cellular and secreted plasminogen activator (PA) levels of 5 cell lines isolated after PbCrO4 treatment are increased up to 8 fold and up to 10 fold respectively as compared to untreated HOS controls. SDS-PAGE analysis in the presence of copolymerized substrates is consistent with increase in 55 kDa urokinase-type PA (u-PA) and 68 kDa tissue-type PA (t-PA). These results show that PbCrO4 treatment leads to stable phenotypic changes indicative of the transformation of HOS cells.
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Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.
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DNA lesions, cytotoxicity, and cellular uptake of CaCrO4 were compared in Chinese hamster ovary, in mouse embryo fibroblast C3H10T1/2, and in human osteosarcoma cells. The concentration of CaCrO4 that reduced colony formation by 50% was 2- or 3-fold less in human osteosarcoma cells than in C3H10T1/2 or Chinese hamster ovary cells. Alkaline elution studies showed that CaCrO4 induced DNA single strand breaks in a concentration dependent manner in all three cell lines. However, the human cells exhibited four times more breaks than the hamster cells and two times more than C3H10T1/2 cells when the CaCrO4 exposure conditions were equivalent. Alkaline elution studies also demonstrated the formation of DNA-protein cross-links by CaCrO4 in all three cell lines. In hamster and mouse cells the induction of these DNA-protein cross-links was dependent on concentrations that ranged from 5 to 50 microM for 6 h; however, the cross-links were saturated at 25 microM in human cells and at 50 microM in mouse and hamster cells. The level of cross-links was four times greater in the human cells compared to the mouse cells and was a factor of 2 greater in the hamster cells compared to the mouse cells. The uptake of CaCrO4 was linear with respect to time and concentration. Uptake of CaCrO4 was equivalent in the human and mouse cells, but was a factor of 4 less in the hamster cells. The single strand breaks were almost entirely repaired after an 18-h incubation in metal free medium in all three cell lines, whereas DNA-protein cross-links persisted in these cell lines in proportion to their initial levels. These results demonstrate differences in the sensitivity of human, hamster, and mouse cells to CaCrO4 and suggest that the repair-resistant DNA-protein cross-link may be important in mediating the long term toxic and carcinogenic effects of CaCrO4.
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