Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer.

A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

Construction noise decreases reproductive efficiency in mice.

Excessive noise is well known to impair rodent health. To better understand the effect of construction noise and to establish effective noise limits during a planned expansion of our vivarium, we analyzed the effects of construction noise on mouse gestation and neonatal growth. Our hypothesis was that high levels of construction noise would reduce the number of live births and retard neonatal growth. Female Swiss Webster mice were individually implanted with 15 B6CBAF1/J embryos and then exposed to 70- and 90-dBA concrete saw cutting noise samples at defined time points during gestation. In addition, groups of mice with litters were exposed to noise at 70, 80, or 90 dBA for 1 h daily during the first week after parturition. Litter size, birth weight, incidence of stillborn pups, and rate of neonatal weight gain were analyzed. Noise decreased reproductive efficiency by decreasing live birth rates and increasing the number of stillborn pups.

Development of a brain nucleus involved in song production in zebra finches (Taeniopygia guttata) is disrupted by Aroclor 1248.

We studied whether polychlorinated biphenyls (PCBs) may alter the development of song control brain nuclei in zebra finch (Taeniopygia guttata) offspring of pulse-exposed hens. We orally administered 40 microg of Aroclor 1248 to adult female finches before egg laying. When the progeny were 50 d old, we measured the volumes of the song control nuclei robustus arcopallialis (RA) and higher vocal center (HVC) using light microscopy. Both male and female progeny of exposed birds had a significantly smaller RA than control birds (36 and 16%, respectively; p < or = 0.05). The HVC did not differ in either sex between exposed and control groups. Perhaps impaired development of RA was caused by PCB action on steroid receptors. We conclude that animals living in contaminated areas may be at risk of neurological damage in hormone-sensitive brain areas and that changes in brain nuclei related to song may be a sensitive indicator of low-level PCB exposure.

Multifactorial relationships between intramammary invasion by Staphylococcus aureus and bovine leukocyte markers.

We explored the hypothesis that the outcome of bacterial invasion (infection or no infection) may depend on immunologic factors when bacterial and environmental factors are kept constant. Leukocyte surface molecules (CD3, CD2, CD4, CD8, CD11b, and CD45r) were assessed before and 3 times after intramammary infusion of Staphylococcus aureus in 5 dairy cows. The somatic cell count (SCC/mL), bacterial count (colony-forming units [CFUs]/mL), ratio of milk phagocytes (mononuclear [Mphi] plus polymorphonuclear [PMN] cells) to lymphocytes (P/L index), and ratio of PMN to Mphi cells (PMN/Mphi index) were determined. Although all cows showed evidence of inflammation resulting from the infusion (the median P/L ratio was 11 times greater 1 d after infusion than before infusion), bacteria were not obtained from the milk of 2 cows. Threshold-like responses, resulting in bacterial counts that approached zero (indicating no infection) and SCCs of less than 500000/mL, were observed when the milk CD2+ lymphocyte proportion exceeded 73% (P < or = 0.007). At 1 d after infusion, 7 immune factors distinguished infected cows from those without infection with more than 95% confidence: compared with infected cows, uninfected cows had higher proportions of CD3+, CD2+, CD4+, and CD8+ T cells, higher densities of CD3 and CD2 molecules per cell, and a higher density of CD11b molecules on milk Mphi cells. At 7 d after infusion, the PMN/Mphi index was lower (94% confidence) in uninfected than in infected cows. At 14 d, the CD2, CD8, and CD45r marker densities were lower than those at 1 d (P < 0.02), findings compatible with memory function. Synergism was suggested by the combined effects of the proportions of CD3+, CD2+, and CD11b+ cells, which explained 75.5% of the bacterial-count variability (P < 0.001); alone, none of these markers predicted CFU variability. These results support further studies aimed at identifying cows capable (or incapable) of early bacterial clearance.

Pathophysiology of white-tailed deer vaccinated with porcine zona pellucida immunocontraceptive.

White-tailed deer (n=14 treated, n=7 control) were examined postmortem to identify any possible pathophysiology resulting from PZP immunocontraception vaccination. Deer were treated twice in 1997; given a booster in 1998, with six being revaccinated in September 2000. Granulomas were found at injection sites of most deer, even 2 years post-treatment. Eosinophilic oophoritis occurred in 6 of 8 (75%) deer vaccinated in 1998, and 3 of 6 (50%) revaccinated in 2000. The 2000 revaccinates without oophoritis, had significantly fewer normal secondary follicles than control females (P=0.03), and deer in the 1998 treatment group (P=0.04). PZP immunocontraceptive vaccine elicited ovarian pathologies in deer similar to those observed in other species.

From dogs to frogs: how pets, laboratory animals, and wildlife aided in elucidating harmful effects arising from a hazardous dumpsite.

The medical literature contains many examples of cases in which serendipitous observations have led to important findings. In the example described in this article, laboratory and field observations conducted at the Mohawk Nation Community of Akwesasne led to the important and unexpected finding that frogs once plentiful in the area were no longer observed. Laboratory tests comparing river sediments from Akwesasne to pristine sediment from Ithaca, NewYork, indicated multiple adverse health effects on developing frogs. Some of the behavioral changes observed in the laboratory were similar to those described by residents of Akwesasne before the onset of amphibian decline. The magnitude of changes paralleled frog body burden of polychlorinated biphenyls acquired from the Akwesasne sediment. The impact of these findings on the identification of a hazardous waste site and global amphibian decline are discussed.

Reproductive impairment in zebra finches (Taeniopygia guttata).

The effects of polychlorinated biphenyls (PCBs) as compounds that may disrupt endocrine activity and, consequently, alter reproductive performance were investigated in altricial zebra finches (Taeniopygia guttata). The breeding performance and breeding cycle of zebra finches differed significantly between nonexposed birds and those experimentally pulse-exposed to Aroclor 1248, a PCB compound (40 microg/bird). Aroclor-exposed birds showed significantly increased numbers of clutches laid, nests constructed per pair, incubation time per pair, and percentage of hatchling mortality compared to controls. Not all reproductive parameters were affected. Those traditionally regarded as indicators of reproductive capacity (number of eggs laid per clutch, number of eggs laid per pair, hatchlings per clutch, and fledglings per clutch) did not differ statistically between exposed and control birds. Findings support the hypothesis that very low PCB doses may be associated with endocrine disruption. It is suggested that evaluation of reproductive parameters related to parental care is more adequate to assess endocrine disruption than is evaluation of reproductive success parameters. Given its short breeding cycle, altricial breeding behavior, and other advantages not possessed by precocial birds, we propose using the zebra finch for evaluations of chemicals with endocrine-disruptive activity.

Impacts of glutathione peroxidase-1 knockout on the protection by injected selenium against the pro-oxidant-induced liver aponecrosis and signaling in selenium-deficient mice.

Previous research has suggested that repletion of cellular glutathione peroxidase (GPX1) activity by a single injection of Se was dissociated from the Se protection against the pro-oxidant-induced liver necrosis in Se-deficient rodents. Using the GPX1 knockout (GPX1-/-) mice, TUNEL assay, and apoptosis gene expression microarray, we have demonstrated strikingly different impacts of GPX1 knockout on hepatotoxicity and the related signaling induced by an intraperitoneal injection of 12.5 mg paraquat/kg body weight (b.wt.). In both Se-deficient GPX1-/- and wild-type (WT) mice, the paraquat did not induce typical liver necrosis, rather aponecrosis or necrapoptosis, a syncretic process of cell death sharing characteristics of both apoptosis and necrosis. The severity of liver aponecrosis and the associated mortality were reduced to a much greater extent by an injection of Se (ip, 50 microg/kg b.wt. as Na2SeO3) prior to paraquat stress in the WT mice, compared with the GPX1-/- mice. The induced liver aponecrosis seemed to be more apoptotic in the GPX1-/- mice but more necrotic in the WT mice. The paraquat-mediated gene or protein expression of proapoptotic Bax, Bcl-w, and Bcl-X(S), cell survival/death factors GADD45, MDM2, c-Myc, and caspase-3 was upregulated, but that of antiapoptotic Bcl-2 was downregulated in the GPX1-/- mice vs. the WT mice. Overall, these differences between the two groups of mice were related to a low level of liver GPX1 activity in the WT mice that represented < 4% of the normal physiological level. Therefore, the low level of GPX1 activity in the Se-deficient mice can exert a potent role in defending against liver aponecrosis induced by moderate oxidative stress.

Lethal and sublethal effects of polychlorinated biphenyls on Rana sylvatica tadpoles.

In static experiments, we exposed tadpoles of the wood frog (Rana sylvatica) to sediment collected from a riverine wetland in the St. Lawrence River basin that is highly contaminated with polychlorinated biphenyls (PCBs). Significant mortality occurred early in the experiment and was not explained by a simple dose-dependent relationship. Direct sediment contact resulted in higher tadpole mortality compared with tadpoles suspended in mesh containers above the sediment. Sublethal effects of exposure were also apparent, characterized by behavioral abnormalities, including reduced activity levels and swimming speed, that differed depending on whether tadpoles were in contact with or suspended above the sediment. We demonstrate in this experiment that PCB-contaminated sediment induced significant mortality and behavioral dysfunction in early development, but the effects on natural populations existing in the contaminated region is not known.