Endothelial cells (EC) produce cytokines, such as interleukin (IL)-1, IL-6, IL-8 and granulocytemacrophage colony-stimulating factor (GM-CSF). These cytokines have an important role in the proliferation and differentiation of hematopoietic progenitor cells. On the other hand, anticancer agents generally cause hematopoietic disorders. However, little is known about the effects of chemotherapeutic agents on the secretion of cytokines from EC. Therefore, we investigated if treatment with platinum compounds may stimulate EC to secrete cytokines. EC newly isolated from a human umbilical vein were exposed to cisplatin, carboplatin, or TRK-710 for 80 min, then the cells were washed and placed in fresh medium. The levels of cytokines in the fresh medium were measured by the ELISA method, the levels of intracellular hydrogen peroxide (H 2 O 2 ) were measured by flow cytometry, and the rhodamine 123-stained live mitochondria of the EC were observed under a confocal laser microscope. Platinum compounds induced cytokine production in human EC: cisplatin most prominently induced the release of IL-1 and IL-6, and TRK-710 had the greatest ability to induce the release of GM-CSF. Intracellular H 2 O 2 production and IL-8 release were transiently induced immediately after treatment with platinum compounds, leading to IL-1 release when H 2 O 2 production was eliminated. These results may provide new insights into the hematological toxicity induced by anticancer agents and the role of IL-1 and IL-6 secreted from EC in this toxicity.
In this study, the authors investigated regional differences in lung cancer mortality in Japan, and, based on data acquired between 1970 and 1990 for 47 Japanese prefectures, estimated the relationship between regional lung cancer mortality and air pollution and/or temperature. Investigators used data for nitrogen dioxide, sulfur dioxide, motor vehicle density, tobacco expenditure, and temperature as independent variables for age-adjusted lung cancer death rates. The age-adjusted lung cancer death rates were higher in the southern geographical block of Japan (i.e., approximately 1.2-fold in males and 1.1-fold in females) and in the northern block (approximately 1.2-fold in males) than in the central block. The regional differences in the age-adjusted lung cancer death rates were explained by nitrogen dioxide and temperature. Temperature caused a greater effect (regression coefficients) of nitrogen dioxide on the age-adjusted lung cancer death rates than did nitrogen dioxide alone in the southern block (i.e., approximately 1.3-fold in males and 1.2-fold in females). These results provide the first evidence of a possible synergistic interaction between air pollution and high temperature on lung cancer mortality.
We used our new flow cytometric method to measure benzo[a]pyrene-diolepoxide-deoxyribonucleic acid adduct levels in peripheral lymphocytes from healthy male smokers and nonsmokers. Smokers who had pack-years of 20 or more had significantly higher mean benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels than nonsmokers. In smokers, the adduct levels were correlated significantly with age, years of smoking, and pack-years, whereas daily tobacco consumption was not correlated with adduct levels. We also found a positive relationship between age and benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels in nonsmokers. Passive exposure to tobacco smoke was not associated with adduct levels. The results of our study indicate that benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels may be closely related to aging and that tobacco smoking-as well as other environmental factors-may play a role in the benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct formation.
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