Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies.

A survey of glycophorin A (gpa) in vivo somatic cell mutation in a population of 394 healthy people from 8 to 77 years of age (mean age +/- SD 41 +/- 15 years) revealed a subset of 37 individuals with stably elevated allele-loss and/or allele-loss with duplication variant erythrocyte frequencies (Vf) exceeding 30 x 10(-6). These 37 individuals with gpa outlier Vf are significantly older (P < 0.001) than the remainder of the larger study population from which they were drawn reflecting a highly significant increase in the prevalence of these individuals in the population beyond age 40 years.

Biodosimetry of Chernobyl cleanup workers from Estonia and Latvia using the glycophorin A in vivo somatic cell mutation assay.

The reactor accident at Chernobyl in 1986 necessitated a massive environmental cleanup that involved over 600,000 workers from all 15 Republics of the former Soviet Union. To determine whether the whole-body radiation received by workers in the course of these decontamination activities resulted in a detectable biological response, over 1,500 blood samples were obtained from cleanup workers sent from two Baltic countries, Estonia and Latvia. Here we report the results of studies of biodosimetry using the glycophorin A (GPA) locus in vivo somatic cell mutation assay applied to 734 blood samples from these workers, to 51 control samples from unexposed Baltic populations and to 94 samples from historical U.

Diagnosis of ataxia telangiectasia with the glycophorin A somatic mutation assay.

There are no widely applied definitive laboratory tests for the diagnosis of ataxia telangiectasia (AT). We, and others, have previously reported significantly elevated levels of in vivo somatic mutation in blood samples from known AT patients, observations that might form the basis for a useful prospective laboratory test for confirmation of a clinical diagnosis of AT. In the present case, a 4 1/2-year-old black female was suspected of having AT based on ataxic gait and chronic upper respiratory infections.

Prediction of an occupational exposure limit for a mixture on the basis of its components: application to metalworking fluids.

Using a previously developed mouse bioassay, a semisynthetic metalworking fluid (MWF "B") and its major components were evaluated. In mice MWF "B" and its components produced both sensory (S) and pulmonary (P) irritation. Using respiratory frequency (f) depression, concentration-response relationships were developed for each component as well as for MWF "B.

A murine model for assessing the respiratory hypersensitivity potential of chemical allergens.

Using equimolar quantities of 2 chemical allergens, toluene diisocyanate (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing activity, the mouse was evaluated as a possible model to indicate respiratory hypersensitivity. A previously published procedure (Garssen et al. (1989) Immunology 68, 51-58) was followed whereby chemicals were applied epicutaneously to the shaved flank of BALB/c mice.

Evaluation of respiratory effects of thermal decomposition products following single and repeated exposures of guinea pigs.

Groups of guinea pigs were exposed to the thermal decomposition products (TDP) released from acrylonitrile butadiene styrene (ABS), polypropylene-polyethylene copolymer (CP), polypropylene homopolymer (HP), or plasticized polyvinyl chloride (PVC). In single 50-min exposures to the TDP, guinea pigs exhibited sensory irritation, coughing, and airways constriction. Significant decreases in respiratory frequency (f) occurred during TDP exposure which were magnified during CO2 challenge conducted immediately post-exposure.

Respiratory responses of mice exposed to thermal decomposition products from polymers heated at and above workplace processing temperatures.

Mice were exposed to thermal decomposition products (TDP) released from acrylonitrile butadiene styrene (ABS), polypropylene-polyethylene copolymer (CP), polypropylene homopolymer (HP), or plasticized polyvinylchloride (PVC). These resins were heated in a temperature programmable furnace, at and above workplace processing temperatures. LC50 and RD50 values were obtained on the basis of resin mass loaded in the furnace.

Correlation of polymorphic expression of CYP2D6 mRNA in bladder mucosa and tumor tissue to in vivo debrisoquine hydroxylase activity.

Debrisoquine hydroxylase activity has been attributed to CYP2D6 and poor metabolizers of debrisoquine have a reduced relative risk of developing aggressive bladder cancer. Production of a proximate carcinogen could occur in liver or bladder mucosa. However, it is not known if CYP2D6 is expressed in human bladder mucosa.

Animal models of occupational asthma.

Occupational asthma is characterized by variable airflow obstruction occurring in the workplace. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Since its pathogenic mechanism(s) are unknown, animal models have been developed to investigate the various disease processes, as well as to enable study of environmental and genetic factors which may contribute to disease development.

Computer programs for calculation of median effective dose (LD50 or ED50) using the method of moving average interpolation.

Over the past 40 years, toxicologists and pharmacologists have used tables published by Weil for the determination of LD50 (or ED50) values and their associated 95% confidence intervals. With the advances in computer technology, it is now common for investigators to have personal computers in their laboratories. Therefore, two identical programs were developed for determination of the LD50 (or ED50) which may be run on a personal computer.