Micronucleated erythrocytes as an index of cytogenetic damage in humans: demographic and dietary factors associated with micronucleated erythrocytes in splenectomized subjects.

Erythrocytes containing micronuclei serve as an indicator of genotoxic exposure in splenectomized individuals. Micronucleated erythrocytes, derived from cytogenetically damaged RBC precursors, are not selectively removed from peripheral blood in individuals who lack splenic function. The relationship between micronucleated cell frequencies and demographic, environmental, and dietary factors was examined in 44 subjects with previous splenectomy due to trauma. Their micronucleated cell counts fit a log-normal distribution, with geometric means of 3.3 micronucleus-containing cells/1000 reticulocytes and 2.7/1000 normochromatic erythrocytes. A multiple regression analysis showed that drinking five cups of coffee or tea/day (relative to none) was associated with an approximately 2-fold higher frequency of micronucleated cells. Weaker statistical associations were also noted with micronucleus frequency and the consumption of calcium supplements (associated with a higher frequency) and vitamins A, C, or E (lower frequency). An apparent trend of higher micronucleus counts with age was attenuated when other factors were considered in the regression. Cigarette smoking and decaffeinated coffee consumption were among the factors not associated with elevated micronucleated cell frequencies. Because the occurrence of micronuclei in reticulocytes reflects cytotoxic exposures within the past 3-8 days, it may be possible to test directly the relationship of these factors to micronucleus formation through intervention studies.

Chronic low-level lead exposure. Its role in the pathogenesis of hypertension.

Lead is a common element in the earth's crust, serving useful purposes in industry, but serving no purpose in the human body. Increase in blood pressure is an important public health problem with numerous factors contributing to many facets of the disease. The relationship of lead exposure and increased blood pressure has long been considered, but only recently critically investigated. Reports of subtle changes in calcium metabolism and renal function, as well as in vitro studies examining end-arteriolar smooth muscle contractility, link lead exposure and increased blood pressure. This paper critically examines the evidence associating chronic low-level lead exposure and increased blood pressure. The review focuses on epidemiological, clinical, and toxicological data. The epidemiological evidence is consistent with low-level exposure to lead causing an elevation in blood pressure. The strength of that association, and the dose-response characteristics, are less certain. Individual resistance and susceptibility could affect the degree of blood pressure elevation. The results of animal and in vitro studies are consistent with the epidemiological evidence, and suggest biologically plausible mechanisms for the association. The most probable mechanisms are intracellular perturbations in calcium metabolism mediated by direct lead effects at the end-arteriole, and indirect effects via renal dysfunction. Better indices of lead exposure and lead activity are needed to quantify these effects in humans. New and safer methods of chelating lead suggest interesting approaches for studying the relationship between lead and hypertension. This link could have significant implications in determining what constitutes a 'safe' level of environmental lead exposure, and whether a proportion of essential hypertension could be 'cured' by chelation therapy.

Pharmacokinetics of CaNa2EDTA and chelation of lead in renal failure.

The pharmacokinetics of 1 gm intramuscular doses of CaNa2 (14C-)EDTA and the chelation of lead (Pb) were studied in 10 subjects with varying degrees of renal function and normal body burdens of Pb. The clearance of CaNa2EDTA significantly correlated with creatinine clearances (CLCR) (r = 0.8373; P = 0.0097). Clearances were decreased in subjects with CLCR less than 70 ml/min as compared with subjects with CLCR greater than 100 ml/min (28 vs. 76 ml/min). Maximum serum CaNa2EDTA concentrations and volume of distribution (Varea) (0.05 to 0.23 L/kg) were similar in all subjects. The Varea is smaller than previously described and is more consistent with other experimental data. Considering all subjects, initial blood Pb concentrations correlated with cumulative urine Pb excretion over 3 days (r = 0.8967; P = 0.0005). Urine Pb excretion did not correlate with measures of renal function or measures of CaNa2EDTA kinetics. Subjects with abnormal CLCR showed significantly greater decreases in blood Pb from day 1 to day 4 (7.0 micrograms/dl vs. 1.2 micrograms/dl) compared with normal subjects. These decreases in blood Pb correlated with CLCR (r = 0.7774; P = 0.138) and urine protein (r = 0.8435; P = 0.0087) but not with urine Pb excretion. Renal dysfunction may alter Pb chelatability, bone-blood Pb reequilibration, PbEDTA distribution, or PbEDTA excretion.

Recent advances in occupational cancer.

The contribution of occupational and environmental exposures to the etiology of cancer is a topic of considerable scientific and public interest. If an occupational environmental exposure is associated with cancer in man, then both the exposure and the disease are preventable by appropriate protection. In order to enhance the awareness and timeliness of new information concerning occupational cancer, the University of California, San Francisco, School of Medicine in conjunction with the Northern California Occupational Health Center and the National Institutes of Occupational Safety and Health, the American Cancer Society sponsored a two day meeting in San Francisco at the end of 1983. Five of the presentations are highlighted in this review. In addition, twenty special questions of clinical relevance concerning occupational and environmental cancers are reviewed with the consensus answers given.

Diagnosis and treatment of Amanita phalloides-type mushroom poisoning: use of thioctic acid.

The number of cases of mushroom poisoning is increasing as a result of the increasing popularity of "wild" mushroom consumption. Amanitin and phalloidin cytotoxins found in some Amanita and Galerina species produce the most severe and frequent life-threatening symptoms of Amanita phalloidestype poisoning. Delay in onset of symptoms, individual susceptibility variation and lack of rapid and reliable identification have contributed to the significant morbidity and mortality of this type of poisoning.A rapid chromatographic assay for identifying the potent cytotoxins and apparently successful management using thioctic acid of two cases of A. phalloides-type mushroom poisoning are reported. All known cases of A. phalloides-type mushroom poisoning treated with thioctic acid in the United States are summarized.