ABSTRACT
The nitric oxide radical (*NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation of peroxynitrite (ONOO-), the reaction product of *NO and the oxygen radical, superoxide. We hypothesize that tobacco-related compounds are cytotoxic and induce quantifiable DNA single-strand breaks in immortalized hamster cheek pouch (POII) cells, and that an amino acid marker of ONOO- injury, namely, 3-nitrotyrosine (3-NT), is detectable in hamster cheek pouch tissues chronically exposed to these compounds. We observed a dose-dependent decrease in POII cell viability with increasing tobacco-related compound concentrations, as well as a dose-dependent increase in DNA strand breaks. Semi-quantitative immunohistochemistry showed intense 3-NT immunoreactivity in hamster tissues treated with tobacco-related compounds compared with controls (p < 0.005). Our results suggest that tobacco-related compounds, including nicotine, are genotoxic, and that 3-NT is a quantifiable marker of ONOO- damage in intact hamster cheek pouch tissues.
Subject(s)
Carcinogens/adverse effects , Mouth Mucosa/drug effects , Oxidative Stress/drug effects , Tobacco, Smokeless/adverse effects , Tyrosine/analogs & derivatives , Animals , Cell Survival/drug effects , Cells, Cultured , Chromatin/drug effects , Cricetinae , DNA Damage , DNA, Single-Stranded/drug effects , Dose-Response Relationship, Drug , Mesocricetus , Mouth Mucosa/pathology , Nicotine/adverse effects , Nitrosamines/adverse effects , Peroxynitrous Acid/adverse effects , Tyrosine/analysisABSTRACT
An increase in the myometrial expression of the prostaglandin (PG) receptors, and especially the PGF(2alpha) receptor (FP), may be an important component of the process initiating preterm labour. In this review of the literature and presentation of new possibilities, evidence will be discussed that demonstrates an increase in mouse uterine FP mRNA occurs at preterm birth whereas uterine PGF(2alpha) concentrations do not increase, suggesting elevated uterine receptor expression and sensitivity is a mechanism for preterm labour initiation. The first examination of the complete human myometrial FP promoter will be described and evidence presented that demonstrates the pro-inflammatory cytokine, interleukin-1beta, stimulates FP mRNA expression. Finally new data showing that administration of a specific FP antagonist delays preterm birth in sheep will be presented.
Subject(s)
Myometrium/physiopathology , Obstetric Labor, Premature/physiopathology , Receptors, Prostaglandin/physiology , Animals , Female , Gene Expression Regulation , Humans , Mice , Mice, Knockout , Obstetric Labor, Premature/genetics , Pregnancy , Promoter Regions, Genetic , Receptors, Prostaglandin/antagonists & inhibitors , Receptors, Prostaglandin/deficiency , Receptors, Prostaglandin/genetics , SheepABSTRACT
An intraruminal selenium (Se) pellet and a subcutaneous depot of barium selenate, equivalent to 1.6 mg Se/kg body weight, were each effective in maintaining increased blood Se concentrations for at least 200 weeks in ewes at pasture. These treatments given to the ewes 23 to 26 weeks before lambing increased the Se status of their lambs for 4 to 6 months.
Subject(s)
Selenium/administration & dosage , Sheep Diseases/prevention & control , Administration, Oral , Animals , Delayed-Action Preparations , Female , Glutathione Peroxidase/blood , Injections, Subcutaneous/veterinary , Male , Milk/analysis , Selenium/blood , Selenium/deficiency , SheepABSTRACT
Bodyweight, plasma vitamin B12 and blood selenium concentrations were monitored in prime lambs given different forms of supplementation at 2 sites in separate years. At the first site treatment groups comprised control, vitamin B12 injection, selenium given orally and a combination of vitamin B12 and selenium. At the second site cobalt and selenium supplied in a glass bullet was compared with an untreated group. Significant sex-related responses were observed to treatment in terms of bodyweight and at site 2 in plasma vitamin B12 concentrations. A marked bodyweight response to glass bullet supplementation was observed in castrated male lambs but not in ewe lambs. These studies show that sex differences should be considered when investigating trace element deficiencies.
