Human nails as a biomarker of arsenic exposure from well water in Inner Mongolia: comparing atomic fluorescence spectrometry and neutron activation analysis.

Arsenic (As) is found naturally in the geological strata within the Ba Men Region of Inner Mongolia, China. A study was conducted to compare the total As measurements from two analytical techniques: instrumental neutron activation analysis (INAA) and atomic fluorescence spectrometry (AFS), and to verify nails as an exposure biomarker in this population. In 1999, nail and water samples were collected in a pilot study. Fingernails and toenails were pooled from 32 participants and analysed for total As by both INAA and AFS. Mean nail As values were 14.8+/-2.4 and 19.4+/-2.8 microg g-1 (+/-SEM) for INAA and AFS, respectively. Results from these two methods were significantly correlated (r=0.93, p<0.0001). In 2000, a second study was conducted and INAA was used to measure total As in toenails from 314 Ba Men residents. Well water samples were collected from 121 households and analysed by AFS. A significant correlation was observed between toenail and well water As (r=0.84, p<0.0001). Based on the results, INAA was significantly correlated with AFS and proved to be a reliable measure of nail As levels. In this population, toenail samples are a useful internal As exposure biomarker from drinking water sources.

Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China.

The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.

Cancer mortality in four northern wheat-producing states.

Chlorophenoxy herbicides are used both in cereal grain agriculture and in nonagricultural settings such as right-of-ways, lawns, and parks. Minnesota, North Dakota, South Dakota, and Montana grow most of the spring and durum wheat produced in the United States. More than 90% of spring and durum wheat is treated with chlorophenoxy herbicides, in contrast to treatment of approximately 30% of winter wheat. In this ecologic study I used wheat acreage as a surrogate for exposure to chlorophenoxy herbicides. I investigated the association of chlorophenoxy herbicides with cancer mortality during 1980-1989 for selected counties based on level of agriculture ([greater and equal to] 20%) and rural population ([greater and equal to] 50%). Age-standardized cancer mortality rates were determined for grouped counties based on tertiles of wheat acreage per county or for individual counties for frequently occurring cancers. The cancer sites that showed positive trends of increasing cancer mortality with increasing wheat acreage were esophagus, stomach, rectum, pancreas, larynx, prostate, kidney and ureter, brain, thyroid, bone, and all cancers (men) and oral cavity and tongue, esophagus, stomach, liver and gall bladder and bile ducts, pancreas, cervix, ovary, bladder, and other urinary organs, and all cancers (women). Rare cancers in men and women and cancers in boys and girls were studied by comparing counties above and below the median of wheat acreage per county. There was increased mortality for cancer of the nose and eye in both men and women, brain and leukemia in both boys and girls, and all cancers in boys. These results suggest an association between cancer mortality and wheat acreage in counties of these four states.

Cancer mortality in agricultural regions of Minnesota.

Because of its unique geology, Minnesota can be divided into four agricultural regions: south-central region one (corn, soybeans); west-central region two (wheat, corn, soybeans); northwest region three (wheat, sugar beets, potatoes); and northeast region four (forested and urban in character). Cancer mortality (1980-1989) in agricultural regions one, two, and three was compared to region four. Using data compiled by the National Center for Health Statistics, cancer mortality was summarized by 5-year age groups, sex, race, and county. Age-standardized mortality rate ratios were calculated for white males and females for all ages combined, and for children aged 0-14. Increased mortality rate ratios and 95% confidence intervals (CIs) were observed for the following cancer sites: region one--lip (men), standardized rate ratio (SRR) = 2.70 (CI, 1.08-6.71); nasopharynx (women), SRR = 3.35 (CI, 1.20-9.31); region two--non-Hodgkin's lymphoma (women), SRR = 1.35 (CI, 1.09-1.66); and region three--prostate (men), SRR = 1.12 (CI, 1.00-1.26); thyroid (men), SRR = 2.95 (CI, 1.35-6.44); bone (men), SRR = 2.09 (CI, 1. 00-4.34); eye (women), SRR = 5.77 (CI, 1.90-17.50). Deficits of smoking-related cancers were noted. Excess cancers reported are consistent with earlier reports of agriculturally related cancers in the midwestern United States. However, reports on thyroid and bone cancer in association with agricultural pesticides are few in number. The highest use of fungicides occurs in region three. Ethylenebisdithiocarbamates, whose metabolite is a known cause of thyroid cancer in rats, are frequently applied. This report provides a rationale for evaluation of the carcinogenic potential of this suspect agent in humans.

Iron intake and the risk of colorectal cancer.

Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period. Subsite analysis showed that the risk of colon cancer due to iron intake was elevated throughout the colon for both men and women, with the highest adjusted risks for the interquartile range seen in the proximal colon for females (relative risk, 1.51; 95% confidence interval, 1.41-1.60). The risk of rectal cancer was not significantly elevated for men or women. Elevated serum iron was also associated with increased risk; however, this effect was strongest in the distal (rather than proximal) colon and was significant only among females (adjusted relative risk, 1.73; 95% confidence interval, 1.03-2.92). The mean transferrin saturation was higher among cases than controls (30.7 versus 28.7%), but total iron-binding capacity did not seem to predict the occurrence of colorectal cancer. Proportional hazards models confirmed that the effects of iron and serum iron were not confounded by age, gender, energy consumption, fat intake, or other known risk factors for colorectal cancer. These data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. These differences may be due to such factors as oxidation state, binding proteins and the presence of other cofactors such as bile acids, products of bacterial metabolism.

Host determinants of cellular and biochemical constituents of bronchoalveolar lavage fluids. Implications for design of epidemiologic studies.

The effects of demographic characteristics, exercise, environmental exposures, and other host factors on cellular and biochemical constituents of human bronchoalveolar lavage (BAL) fluids were investigated by studying more than 300 specimens obtained from normal volunteers and assayed in a single center. The BAL data demonstrated associations with race, smoking, exercise, skin-test reactions, and blood constituents, and weak or no associations with age, sex, pulmonary function tests (PFT), or ambient ozone exposure. The effect of exercise was relatively strong and more clearly characterized than in previous studies. Smoking effects were similar to those observed in other studies; our ability to study age and ambient ozone effects was greatly limited because of the homogeneity of the population under study. Blood constituents of the subjects also showed an association with level of exercise. Analysis of intraindividual and interindividual variability in BAL constituents results suggested that matching, although desirable, is not essential for the maintenance of adequate statistical power in BAL studies, so observational studies of the effects from air pollution on BAL fluids in humans could be effectively conducted using cross-sectional designs.

Aspirin use and lung, colon, and breast cancer incidence in a prospective study.

A large body of experimental data and several recent epidemiologic studies indicate that aspirin use may decrease cancer risk. The experimental studies found effects at many anatomic sites, whereas the epidemiologic studies saw the greatest effect on mortality from digestive cancers. To provide further human data, we examined the association between aspirin use and cancer risk using data from the National Health and Nutrition Examination Survey I (NHANES I) and the NHANES I Epidemiologic Follow-up Studies (NHEFS). Characterization of aspirin use was based on questions in the baseline interview asking whether subjects used aspirin during the previous 30 days. Data were available from 12,668 subjects age 25-74, at time of initial examination for NHANES I, who were followed for an average of 12.4 years. Among these subjects, 1,257 were diagnosed with cancer more than 2 years after their NHANES I examination. Incidence of several cancers was lower among persons who reported aspirin use: the incidence rate ratios (and 95% confidence intervals) for all sites combined were 0.83 (0.74-0.93), lung cancer 0.68 (0.49-0.94), breast cancer in women 0.70 (0.50-0.96), and colorectal cancer in younger men 0.35 (0.17-0.73). These findings were not readily explained by potentially confounding factors. The data suggest an association between aspirin consumption and decreased cancer incidence at several cancer sites.

Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung.

An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

Effects of 5-bromo-2-deoxyuridine concentration and alpha-naphthoflavone on the association between smoking and the frequency of sister-chromatid exchanges in lymphocytes from maternal and cord blood.

The frequency of sister-chromatid exchanges was analyzed in maternal and cord blood lymphocytes obtained at delivery from 23 nonsmokers and 21 smokers. Lymphocytes were cultured under 3 conditions: in the presence of 100 microM 5-bromo-2-deoxyuridine (BUdR), 20 microM BUdR and 20 microM BUdR with 40 microM alpha-naphthoflavone (ANF). Under all assay conditions, frequencies of SCEs were consistently higher for maternal lymphocytes than for cord lymphocytes. There was no association between SCE values for cultures of the same blood specimen with 100 microM BUdR and 20 microM BUdR. When cultured with 100 microM BUdR, maternal lymphocytes from smokers had a mean SCE frequency of 13.5, which was significantly higher than the value of 11.1 observed for nonsmokers (p = 0.001 by the Wilcoxon rank sum test). Maternal smoking had no significant effect on overall frequencies of SCEs in maternal blood cultured with 20 microM BUdR either with or without ANF or when the differential between cells cultured with and without ANF was considered. Use of caffeinated beverages was associated with increased SCE values for maternal lymphocytes cultured with 20 microM BUdR (Tau beta = 0.36, p = 0.02 for the Kendall's Rank Correlation), but no such association was seen with 100 microM BUdR. For cord blood lymphocytes, however, neither smoking nor caffeine use were associated with SCE values obtained by any of the assay conditions used. The findings suggest that results of human monitoring studies using SCEs could differ depending on the concentration of BUdR used in cultures.