Research Triangle Park

About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.

Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.

Abstract: This report reviews the literature on the genotoxicity of mainstream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it has been tested, with the base/neutral fractions being the most mutagenic. In rodents, cigarette smoke induces sister chromatid exchanges (SCEs) and micronuclei in bone marrow and lung cells. In humans, newborns of smoking mothers have elevated frequencies of HPRT mutants, translocations, and DNA strand breaks. Sperm of smokers have elevated frequencies of aneuploidy, DNA adducts, strand breaks, and oxidative damage. Smoking also produces mutagenic cervical mucus, micronuclei in cervical epithelial cells, and genotoxic amniotic fluid. These data suggest that tobacco smoke may be a human germ-cell mutagen. Tobacco smoke produces mutagenic urine, and it is a human somatic-cell mutagen, producing HPRT mutations, SCEs, microsatellite instability, and DNA damage in a variety of tissues. Of the 11 organ sites at which smoking causes cancer in humans, smoking-associated genotoxic effects have been found in all eight that have been examined thus far: oral/nasal, esophagus, pharynx/larynx, lung, pancreas, myeoloid organs, bladder/ureter, uterine cervix. Lung tumors of smokers contain a high frequency and unique spectrum of TP53 and KRAS mutations, reflective of the PAH (and possibly other) compounds in the smoke. Further studies are needed to clarify the modulation of the genotoxicity of tobacco smoke by various genetic polymorphisms. These data support a model of tobacco smoke carcinogenesis in which the components of tobacco smoke induce mutations that accumulate in a field of tissue that, through selection, drive the carcinogenic process. Most of the data reviewed here are from studies of human smokers. Thus, their relevance to humans cannot be denied, and their explanatory powers not easily dismissed. Tobacco smoke is now the most extreme example of a systemic human mutagen.

Orphan nuclear receptors: shifting endocrinology into reverse.

Abstract: Steroid and thyroid hormones and vitamin A metabolites (retinoids) regulate the expression of complex gene programs by binding to members of the nuclear receptor family of ligand-activated transcription factors. The nuclear receptor family also includes many "orphan" members that currently lack known ligands but that represent candidate receptors for new hormones. Recently, natural and synthetic ligands have been identified for several orphan receptors and used to dissect their biological roles. This "reverse endocrinology" strategy has resulted in the discovery of unanticipated nuclear signaling pathways for retinoids, fatty acids, eicosanoids, and steroids with important physiological and pharmacological ramifications.

Getting to the Truth: Evaluating National Tobacco Countermarketing Campaigns

Abstract: Objectives. This study examines how the American Legacy Foundation's “truth” campaign and Philip Morris's “Think. Don't Smoke” campaign have influenced youths' attitudes, beliefs, and intentions toward tobacco. Methods. We analyzed 2 telephone surveys of 12- to 17-year-olds with multivariate logistic regressions: a baseline survey conducted before the launch of “truth” and a second survey 10 months into the “truth” campaign. Results. Exposure to “truth” countermarketing advertisements was consistently associated with an increase in anti-tobacco attitudes and beliefs, whereas exposure to Philip Morris advertisements generally was not. In addition, those exposed to Philip Morris advertisements were more likely to be open to the idea of smoking. Conclusions. Whereas exposure to the “truth” campaign positively changed youths' attitudes toward tobacco, the Philip Morris campaign had a counterproductive influence. (Am J Public Health. 2002;92:901–907)

Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Abstract: Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system.