Comparative stochastic effects of alpha, beta or x-irradiation of the lung of rats.

The stochastic effects in the lung of inhaled, insoluble particles of alpha- and beta-emitting particles and low-linear energy transfer (LET) thoracic irradiation were compared in rats using data from previously conducted studies. Male and female F344 rats were exposed briefly by nasal inhalation to relatively insoluble aerosols of CeO(2) or PuO(2) to achieve a range of four lung burdens. The mean lifetime beta doses to the lung were 3.

Carcinogenic interactions between a single inhalation of 239PuO2 and chronic exposure to cigarette smoke in rats.

Rats were exposed once by inhalation to plutonium-239 dioxide ((239)PuO(2)), resulting in chronic alpha-particle irradiation of the lung, and exposed chronically to cigarette smoke to examine carcinogenic interactions between the two exposures. F344 rats were exposed to (239)PuO(2) to achieve an initial lung burden of 0.5 kBq and then exposed 6 h/day, 5 days/week to cigarette smoke at 100 or 250 mg particulate matter/m(3) for up to 30 months.

Radiological risk assessment of Capstone depleted uranium aerosols.

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models.

Assessing the renal toxicity of Capstone depleted uranium oxides and other uranium compounds.

The primary target for uranium toxicity is the kidney. The most frequently used guideline for uranium kidney burdens is the International Commission on Radiological Protection value of 3 microg U g(-1) kidney, a value that is based largely upon chronic studies in animals. In the present effort, a risk model equation was developed to assess potential outcomes of acute uranium exposure.

Radiotoxicity of inhaled (239)PuO(2) in dogs.

Beagle dogs inhaled graded exposure levels of insoluble plutonium dioxide ((239)PuO(2)) aerosols in one of three monodisperse particle sizes at the Lovelace Respiratory Research Institute (LRRI) to study the life-span health effects of different degrees of alpha-particle dose non-uniformity in the lung. The primary noncarcinogenic effects seen were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, and radiation pneumonitis and pulmonary fibrosis. Radiation pneumonitis/ pulmonary fibrosis occurred from 105 days to more than 11 years after exposure, with the lowest associated alpha-particle dose being 5.

Histopathology of the urinary bladders of cynomolgus monkeys treated with PPAR agonists.

Peroxisome proliferator-activated receptors (PPAR) are involved in the pathogenesis of insulin resistance, diabetes, hyperlipidemias, and related complications. Consequently, a mechanistic understanding of PPAR subtypes and their activation provides promising therapeutic targets for the management of type 2 diabetes mellitus and the metabolic syndrome. Available data from rodent carcinogenicity studies, however, demonstrate that PPAR agonists can be tumorigenic in one or more species of rodents at multiple sites.

Role of muscarinic receptors in the regulation of immune and inflammatory responses.

Leukocytes contain both nicotinic and muscarinic receptors, and while activation of nicotinic receptors suppresses immune/inflammatory responses, the role of muscarinic receptors in immunity is unclear. We examined the effects of a muscarinic receptor antagonist (atropine) and agonist (oxotremorine), administered chronically through miniosmotic pumps, on immune/inflammatory responses in the rat. Results show that while oxotremorine stimulated, atropine inhibited the antibody and T-cell proliferative responses.

A review of the histopathology of cigarette smoke-induced lung cancer in rats and mice.

In the past several years an increased number of lung tumors has been reported in laboratory studies of rats and mice after lifetime exposure to mainstream cigarette smoke. Proliferative epithelial lesions are present in the lungs of both species and are apparent antecedent lesions to benign and malignant tumors. Both species have alveolar epithelia hyperplasia, alveolar adenomas, and alveolar carcinomas.

Transplacental carcinogenicity of 3'-azido-3'-deoxythymidine in B6C3F1 mice and F344 rats.

The prophylactic use of zidovudine (3'-azido-3'-deoxythymidine, AZT) during pregnancy greatly reduces transmission of HIV-1 from infected mothers to their infants; however, the affinity of host cell DNA polymerases for AZT also allows for its incorporation into host cell DNA, predisposing to cancer development. To expand upon previous transplacental carcinogenesis assays performed in CD-1 mice, the transplacental carcinogenicity of AZT was evaluated in a second mouse strain and a second rodent species. Date-mated female mice and rats were gavaged daily with 0, 80, 240, or 480 mg AZT/kg bw during the last 7 days of gestation.

Comparative pathology of environmental lung disease: an overview.

Environmental factors play a major role in a majority of lung diseases. Asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and many interstitial lung diseases are influenced or caused by environmental factors. Animals and humans may respond differently to the same agent, and a study of the comparative pathology between the two is useful for optimizing animal models of environmental lung disease and for evaluating their predictive value in carcinogenicity studies.

Comparative oncology of lung tumors.

Toxicologic pathologists need to understand the comparative oncology of lung tumors because lung cancer is a common and serious cancer in the human population. Lung cancer in humans is known to be caused by cigarette smoke and a number of other carcinogens in the environment. Animal studies are needed to elucidate possible interactions with other potential carcinogens in environmental or occupational settings.

Particle size and composition related to adverse health effects in aged, sensitive rats.

Small increases in concentrations of ambient particulate matter (PM*) have been linked to adverse health effects, especially in older people and people with preexisting respiratory disease. Some epidemiologic studies have shown the association to be stronger with PM less than 2.5 microm in aerodynamic diameter (PM2.

Low-level subchronic exposure to wood smoke exacerbates inflammatory responses in allergic rats.

Epidemiological studies have implicated wood smoke as a risk factor for exacerbating asthma. However, comparisons of findings in animal models with those in humans are currently not possible, because detailed clinically relevant measurements of pulmonary function are not available in animal studies. Brown Norway rats were immunized with ovalbumin and exposed to either filtered air or wood smoke at 1 mg particulate matter/m(3) for 70 days and challenged with allergen during the last 4 days of exposure.

Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer in B6C3F1 mice through genetic and epigenetic pathways.

Although cigarette smoke has been epidemiologically associated with lung cancer in humans for many years, animal models of cigarette smoke-induced lung cancer have been lacking. This study demonstrated that life time whole body exposures of female B6C3F1 mice to mainstream cigarette smoke at 250 mg total particulate matter/m(3) for 6 h per day, 5 days a week induces marked increases in the incidence of focal alveolar hyperplasias, pulmonary adenomas, papillomas and adenocarcinomas. Cigarette smoke-exposed mice (n = 330) had a 10-fold increase in the incidence of hyperplastic lesions, and a 4.

Inhalation toxicity of brevetoxin 3 in rats exposed for twenty-two days.

Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf.

Chronic nicotine inhibits inflammation and promotes influenza infection.

Epidemiological data suggest an association between smoking, respiratory infections, and impaired wound healing. Inflammation is critical in the body's defense against pathogens and in the wound-healing process. Although nicotine is used to treat some inflammatory conditions, the mechanism of this action is largely unknown.

Persistence of mitochondrial toxicity in hearts of female B6C3F1 mice exposed in utero to 3'-azido-3'-deoxythymidine.

Cardiac toxicity has been associated with HIV infection and exposure to nucleoside reverse transcriptase inhibitors (NRTIs), but the role of the latter in the development of cardiac disease of HIV-infected patients is uncertain. To investigate the cardiotoxicity of transplacentally administered zidovudine (AZT) or AZT plus lamivudine (3TC) in the absence of HIV infection, we evaluated several biomarkers of cardiac mitochondrial structure and cardiac structure and function in a B6C3F1 mouse model. In utero exposure to AZT-3TC resulted in ultrastructural pathology, loss of mitochondria, and altered echocardiographic measurements in newborn mice.

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C).

A biphasic response to silica: I. Immunostimulation is restricted to the early stage of silicosis in lewis rats.

Inhalation of crystalline silica may lead to acute or chronic silicosis. Although chronic silicosis is associated with increased incidence/exacerbation of autoimmune disorders, the immunologic effects of chronic silicosis are not completely understood. In an animal model of chronic silicosis, Lewis rats were exposed to filtered air or silica (1.

Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats.

In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues.

Health effects of subchronic exposure to low levels of wood smoke in rats.

Wood smoke is a significant source of air pollution in many parts of the United States, and epidemiological data suggest a causal relationship between elevated wood smoke levels and health effects. The present study was designed to provide information on the potential respiratory health responses to subchronic wood smoke exposures in a Native American community in New Mexico. Therefore, this study used the same type of wood under similar burning conditions and wood smoke particle concentrations to mimic the conditions observed in this community.