Prostate Cancer Risk Through Exposure to Halogenated Hydrocarbons and Modulation by Dietary Supplementation

摘要

A high androgen level, oxidative stress, and low levels of selenium were identified as possible risk factors in prostate cancer development. Halogenated compounds may produce all these effects. Our hypothesis is that halogenated compounds may increase prostate cancer risk through these mechanisms. To test this hypothesis and to develop protection for exposed men, we propose to a) measure enzyme activities and antioxidant levels in PCB-exposed rats, b) determine possible co-carcinogenic factors like low selenium or high fat diets, c) study the mechanisms involved with prostate cancer cells in culture, and d) develop chemopreventive strategies. During this first year of our studies we found that 1) in in vivo studies substituting bromine for chlorine makes biphenyls more health damaging, indicating that brominated pesticides may deserve attention, 2) complex changes in lipid homeostasis, vitamin levels and redox status occur that need to be carefully taken into consideration, 3) cell culture experiments with prostate cells should use more than one pair of androgen sensitive/androgen insensitive cells, to avoid misleading conclusions, 4) a-tocopheryl quinone may be the most promising biomarker of oxidative stress by halogenated hydrocarbons. Overall these results provide a firm scientific basis for the work that is proposed and will follow.