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Biomedical subjects

R O McClellan

Publications and source records attributed to R O McClellan.

At least 91 records · Page 5Linked to original sources

Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity.

The respiratory tract epithelium of dogs, from the nose to the lungs, was examined for cytochrome P-450 and associated biotransformation activities. In the ethmoturbinates, where olfactory epithelium is located, the amount of cytochrome P-450 was comparable to that in the liver, when measured on the basis of activity per milligram of microsomal protein. The rest of the nasal region also contained large quantities of cytochrome P-450. The presence of these enzymes in the nose may be important in chemical-induced tumorigenesis. The nasal carcinogen hexamethyl-phosphoramide was shown to be metabolized by nasal microsomal enzymes to another nasal carcinogen, formaldehyde.

Animals↗

Cytotoxicity of diesel exhaust particle extract--a comparison among five diesel passenger cars of different manufactures.

The cytotoxicity of the dichloromethane extracts of diesel exhaust particles from passenger cars of different manufactures was studied in cultured chinese hamster ovary cells. While exhaust particles from diesel cars of the same make and model yielded extracts of similar cytotoxicity, those from cars of different manufactures yielded extracts with a 3-fold difference in cytotoxicity. Using data on the percentages of extractable organic chemicals and total exhaust particulate emission rates, the emission rate of cytotoxin into the environment from the different cars were calculated. Of the 3 factors that could affect the emission rate of cytotoxins (cytotoxicity of the extractable chemicals, amount of cytotoxins per particle, and particulate emission rate), the differences in particulate emission rates were found to be the predominant factors leading to the differences in the emission rate of cytotoxins. Our findings indicate the need to consider other chemical and physical data, not just the activities of the extracts, when the potential health risk due to the exhaust emissions of different automobiles are compared.

Animals↗

Inhalation toxicology of diesel exhaust particles.

Our present knowledge of the health effects of diesel exhaust particles can be summarized as follows: 1. Diesel exhaust particles are very small in size and consist of a carbonaceous core with a myriad of adsorbed hydrocarbon compounds that are readily extracted with organic solvents. 2. The particle extracts are cytotoxic and mutagenic in in vitro bacterial and mammalian cell cultures. 3. The particle extracts area carcinogenic when painted on mouse skin along with a suitable promoter. 4. Inhaled particles readily deposit in the respiratory tract, a portion is rapidly cleared and a substantial portion is retained for long periods of time (over 100 days) in the lung. 5. Adsorbed hydrocarbon compounds slowly dissociate from the particles in biological media and presumably in the lung. 6. Detoxification mechanisms act on the hydrocarbon compounds released from the particles to minimize effects in in vitro systems and presumably in vivo.

Air Pollutants↗

Primary bone neoplasms in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide.

Primary bone neoplasms developed in beagle dogs briefly exposed by inhalation to aerosols of 238PuO2. 238PuO2 was initially deposited in the respiratory tract where it was retained with a half time greater than 100 days. A portion of the 238Pu was solubilized and translocated to the liver and skeleton. Five years after exposure, 46 osteosarcomas developed in 35 of 144 exposed dogs. The cumulative absorbed radiation doses to skeleton for these dogs ranged from 210 to 830 rad. Of the 46 bone tumors, 22 originated in the vertebrae, 12 in the humeri, 6 in the pelves, and 6 in miscellaneous long and flat bones. Most of the tumors were well-differentiated sarcomas. Only 10 of the tumors metastasized; the lung was the organ most often invaded. Bone tumors were associated with lesions of radiation osteodysplasia. The number of bone tumors found in this study indicated that inhaled 238PuO2 was an effective skeletal carcinogen. The rate of solubilization in the lung and translocation to bone may be a factor in the radiation dose pattern and type and location of bone tumors that developed after inhalation of 238PuO2.

Aerosols↗

Absorption of diethylenetriaminepentaacetic acid (DTPA) from the respiratory tracts of beagle dogs.

Absorption of diethylenetriaminepentaacetic acid (DTPA) from the nasopharyngeal (NP), tracheobronchial (TB) and pulmonary (P) regions of beagle dogs was determined because of the current interest in aerosolized DTPA as a method for the removal of radionuclides deposited in the respiratory tract. Radiolabled DTPA was instilled into the NP, TB and P regions of dogs and its subsequent translocation was followed for 48 hours. Results revealed that 16, 48 and 90% of the instilled DTPA was absorbed into the circulatory system from the NP, TB and P regions, respectively. A comparison was also made between NP absorption of aerosolized as opposed to instilled DTPA. Nasopharyngeal absorption (23%) of aerosolized DTPA was slightly higher than that of instilled DTPA. Further, DTPA deposited in the respiratory tract remained in the body longer than intravenously injected DTPA. These findings indicate that a substantial quantity of DTPA is absorbed from all regions of the respiratory tract and that DTPA need not be deposited within the deep lung to produce systemic absorption of DTPA for the removal of internally deposited radioactive isotopes.

Aerosols↗