Those Pesky Proliferators
A set of nongenotoxic chemicals that cause specific organotoxicity in a variety of tissues is classified as peroxisome proliferators. Toxicity can occur when enzymes in the peroxisomes metabolize fatty acids to produce hydrogen peroxide. Chemicals that act as peroxisome proliferators, including drugs like clofibrate, pesticides like 2,4-D, and industrial chemicals like trichloroethylene, increase cell numbers, peroxisomes, and the size of the liver and, upon repeated exposure, cause liver cancer in rodents. The issue is whether these chemicals also cause cancer in humans. The evidence for and against the human carcinogenicity of peroxisome proliferators is presented in the Focus article on p. 232.
Chemical Effects on Immunity
Many chemicals are known to be genotoxic, carcinogenic, and exert a variety of adverse health effects, but to what extent do they affect the immune system? The second Focus article (p. 236) gives an overview of the immune system and explores the known and potential effects of chemical exposures. Hypersensitivity, autoimmunity, and immunosuppression due to chemicals may play a role in the development and progression of diseases such as cancer and AIDS.
DNA Analysis with Microchips
Jules Verne never thought of this, nor did Michael Creighton. Imagine a microchip loaded with oligonucleotides that can be used to analyze a drop of blood for specific genetic codes in less than two hours. This is not Isaac Asimov, it's Affymetrix's GeneChip technology. This month's Innovations article (p. 244) describes a cooperative project between industry and academia, the importance of which can best be gauged by the multimillion dollar grant awarded. Applications of the GeneChip range from DNA analysis for criminal investigations to individual screening for inherited genetic diseases like cystic fibrosis. New technologies in molecular biology, which are keeping pace with the Human Genome Project, should revolutionize the fields of medicine and environmental health.
ALAD Gene and Lead Toxicity
Smith et al. (p. 248) measured blood lead concentrations in 691 carpenter and joiner union members and bone lead in a subset of 122 subjects. Blood lead averaged 7.78 µg/dl. ALAD genotyping showed there were 591 ALAD 1-1 homozygotes, 95 ALAD 1-2 heterozygotes, and 2 ALAD 2-2 homozygotes in the sample population. When the ALAD 1-2 and 2-2 groups were combined, the data indicated a potential association between elevated bone lead, blood urea nitrogen, and uric acid concentrations in individuals with an ALAD 2 allele, suggesting a possible genetic influence on lead pharmacokinetics and chronic renal toxicity.
Tracheal Cell Metabolism
Rat tracheal epithelial (RTE) cells in various stages of differentiation were cultured in the presence or absence of retinoic acid to investigate metabolic activity after exposure to toxic polycylic aromatic hydrocarbons like TCDD. Castonguay et al. (p. 254) examined the expression of several xenobiotic enzymes like cytochrome P450 isozymes, NADPH-cytochrome P450 reductase, flavin-containing monooxygenase, or glutathione S-transferases as indicators of metabolic activity and demonstrated the presence of both activating and deactivating metabolic enzymes in RTE cells. The authors propose this in vitro test system as a means for screening agents useful in carcinogen detoxification.
Rat Liver Repair
Mangipudy et al. (p. 260) used an animal model to investigate tissue repair. Liver repair processes in rats treated with the hepatotoxin thioacetamide were estimated by measuring cell division and protein synthetic responses. Severe damage was signaled by release of liver-specific enzymes into the serum. The data suggest that the magnitude and time of injury is critical for the repair processes and for determination of animal survival. The authors hypothesize that measurement of tissue repair and injury as simultaneous biological responses to toxic agents could enhance the usefulness of dose-response paradigms for predictive toxicology or for risk assessment.
Asbestos and Genotoxicity
Fibroblast cells from Syrian hamster embryos (SHE) were exposed to asbestos fibers in vitro to investigate primary mechanisms of fiber-induced carcinogenesis. Dopp et al. (p. 268) measured the extent and type of mitotic disturbances and micronucleus induction after SHE cell exposure to amosite, crocidolite, or chrysotile asbestos fibers. The data suggest that asbestos fibers may cause loss and breakage of chromosomes, without directly affecting spindle fibers in the genetic apparatus.
PBB Half-Life in Humans
After accidental exposure of residents in Michigan to polybrominated biphenyls (PBB) in the food chain, public concern about potential long-term health effects prompted studies of the persistence of these compounds. Rosen et al. (p. 272) examined a cohort of 3,877 exposed individuals to determine persistence of the chemical in blood. There were 163 subjects selected with initial PBB levels 20 parts per billion; the median PBB level in this group was 45.5 parts per billion. Estimates indicate that it would take 10.8 years for removal of half of the PBB and that it would take over 60 years to reduce the blood concentration to 1 part per billion.
Soil Ingestion by Children
Accurate estimates of soil ingestion in children are important because of their propensity for hand-to-mouth transfer and potential toxic exposure. Stanek and Calabrese (p. 276) present a methodology to estimate soil ingestion using a model that fits soil ingestion kinetics, reduces variability, minimizes tracer-specific discrepancies, and that is based on a physical mass-balance equation. Although limited by an earlier study protocol used to derive the data, their findings suggest that children may ingest nine times more soil daily than the value currently used by the EPA (200 mg/day) for risk assessment purposes.
Air Pollution and the ER
Xu et al. (p. 286) compared records of physician or emergency room visits with air pollution data in Beijing, China. Household coal stoves used for cooking and heating constitute the major source of air pollutants. A time-series analyses suggested a strong association between sulfur dioxide, total solid particulates, and hospital outpatient visits during winter periods of high air pollution as well as during summer periods of lower air pollution, even though pollutant levels are below World Health Organization recommended air quality standards.