BackgroundObservations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility.ObjectiveOur objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol.MethodsWe examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status.ResultsCompared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002).ConclusionWe observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

An anthelminthic, pyrvinium pamoate (PP), 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, has been found to be extremely toxic to PANC-1 cells in glucose-free medium, but not to be toxic to the same cells cultured in ordinary medium, Dulbecco's modified Eagle's medium (DMEM). It showed the same preferential toxicity for various cancer cell lines during glucose starvation. When 0.1 µ µ µ µg/ml PP was added to the medium, spheroid growth of human colon cancer cell line WiDr was strongly inhibited to a diameter of 750 µ µ µ µm, and this finding is consistent with the concept of antiausterity. PP was also found to exert antitumor activity against human pancreatic cancer cell line PANC-1 in nude mice and SCID mice when it was administered subcutaneously or orally. Regarding the mechanism of PP action, inhibition of Akt phosphorylation, which has been found to be essential for the austerity mechanism, was observed in vitro and in vivo. These findings indicate that PP may be useful for anticancer therapy and that antiausterity therapy could be a novel strategy for anticancer therapy. (Cancer Sci 2004; 95: 685-690) uman cancers arise through many steps of carcinogenesis in which multiple genetic alterations, genetic or epigenetic, are often observed.

among both H. pylori-positive and -negative subjects in Japan.

Background: Although accumulating evidence suggests that Helicobacter pylori plays a role in gastric carcinogenesis, the magnitude of the risk remains uncertain. Aim: We aimed to estimate the magnitude of the risk of gastric cancer associated with H. pylori infection by a large case-control study nested within a prospective cohort. Possible effect modification by CagA status, and serum pepsinogen status, as a marker of atrophic gastritis, was also considered to see its effect on developing gastric cancer. Subjects and Methods: Subjects (n = 123,576) were followed up from 1990 to 2004; 511 gastric cancer cases matched to 511 controls were used in the analysis. Plasma immunoglobulin G antibody to H. pylori, CagA, and pepsinogen I and II were measured.

The development of new strategies designed to detect DNA damage caused by oxidative stress and other means may advance our understanding of the roles of such types of damage in the etiology of cancers, in aging processes, and as biomarkers of exposure. A DNA adduct detection method that uses liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) to detect multiple DNA adducts in human lung tissue is reported herein. This adductome analysis strategy is designed to detect the neutral loss of 2 -deoxyribose from positively ionized 2 -deoxynucleoside adducts in multiple reaction ion monitoring mode (MRM) transmitting the [M + H](+) > [M + H - 116](+) transition over a total of 374 transitions in the mass range from m/z 228.8 to m/z 602.8. Data analysis is optimized and coupled with a comprehensive manual screening process designed to minimize the number of artifactual adducts appearing in the final analysis. In the final analysis, putative adducts were organized into an adductome map and unambiguous confirmation of selected oxidative adducts were made by stable isotope dilution and comparison to authentic standards. The future applications of this method are discussed.