Reduction of the Body Burden of PCBs and DDE by Dietary Intervention in a Randomized Trial

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 noncoplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (−0.0829±0.0357 and −0.00864±0.0116 year−1, respectively; P=.04), but not during VO consumption (−0.0413±0.0408 and −0.0283±0.0096 year−1, respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend \u3c 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. Conclusions In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis

Alcohol drinking in MCH receptor-1-deficient mice

Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance of this finding is unclear, we tested the hypothesis that endogenous MCH signaling enhances alcohol consumption. Methods: Alcohol intake was assessed in male and female wildtype (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice were given 24-hour access to a series of alcohol-containing solutions. Following this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice were allowed 24-hour access to sucrose/quinine as a caloric control and a means to assess taste preference. A naive cohort of male WT and KO mice was tested for alcohol clearance following intraperitoneal administration of 3 g/kg alcohol. Another naive cohort of female mice was utilized to confirm that intracerebroventricular administration of MCH (5 mu g) would augment alcohol drinking in mice. Results: Exogenous MCH enhanced 10% alcohol consumption in mice (saline=0.45 +/- 0.08 g/kg, 5 mu g MCH=0.94 +/- 0.20 g/kg). Male KO mice consumed more 10% alcohol (11.50 +/- 1.31 g/kg) than WT (6.26 +/- 1.23 g/kg) and HET mice (6.49 +/- 1.23 g/kg) during ad libitum access. However, alcohol intake was similar among genotypes during 1 hour daily access. Male KO mice tended to consume less 17.75% sucrose+1.3 mM quinine than controls (WT=10.5 +/- 3.6, HET=7.5 +/- 1.7, KO=4.4 +/- 0.9 g/kg). Alcohol metabolism was similar between WT and KO mice. Conclusions: The finding that male KO consume more alcohol than WT and HET mice, are reminiscent of the counterintuitive reports that KO mice are hyperphagic and yet eat more when administered exogenous MCH. Changes in taste preference or alcohol metabolism do not appear to be important for the increased alcohol drinking in KO mice