Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States.

BACKGROUND: Exposure to endocrine disruptors (EDs), including some phthalates, phytoestrogens and phenols can be quantified using biomarkers of exposure. However, reliability in the use of these biomarkers requires an understanding of the timeframe of exposure represented by one measurement. Data on the temporal variability of ED biomarkers are sparse, especially among children. OBJECTIVE: To evaluate intraindividual temporal variability in 19 individual urinary biomarkers (eight phthalate metabolites from six phthalate diesters, six phytoestrogens (two lignans and four isoflavones) and five phenols) among New York City children. METHODS: Healthy Hispanic and Black children (N=35; 6-10 years old) donated several urine samples over 6 months. To assess temporal variability we used three statistical methods: intraclass correlation coefficient (ICC), Spearman correlation coefficients (SCC) between concentrations measured at different timepoints, and surrogate category analysis to determine how well the tertile categories based on a single measurement represented a 6-month average concentration. RESULTS: Surrogate category analysis indicated that a single sample provides reliable ranking for all analytes; at least three of four surrogate samples predicted the 6-month mean concentration. Of the 19 analytes, the ICC was >0.2 for 18 analytes and >0.3 for 10 analytes. Correlations among sample concentrations throughout the 6-month period were observed for all analytes; 14 analyte concentrations were correlated at 16 weeks. CONCLUSIONS: The reasonable degree of temporal reliability and the wide range of concentrations of phthalate metabolites, phytoestrogens and phenols suggest that these biomarkers are appropriate for use in epidemiologic studies of environmental exposures in relation to health outcomes in children.

Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes.

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. We did not see such changes in lymphocytes from control individuals samples at the same time but not taking vitamin C supplements. This bleomycin assay has been proposed as a test for cancer susceptibility. A similar assay for genetic instability may be useful in detecting heterozygotes for chromosome-breakage syndromes (for example, Fanconi anemia or ataxia telangiectasia). Even though our sample size is small and our results should be interpreted cautiously, statistically significant effects were found with vitamin C supplementation. It would, therefore, be prudent to consider dietary and perhaps other lifestyle factors when interpreting of results from this bleomycin assay and related assays for genetic instability.

Increased chromosome fragility as a consequence of blood folate levels, smoking status, and coffee consumption.

Chromosome fragility in 96 h, low-folate cultures was found to be associated with smoking status, coffee consumption, and blood folate level. The higher proportion of cells with chromosome aberrations in cigarette smokers was attributable to lower red cell folate levels in smokers compared with nonsmokers. There was a positive linear relationship between the average cups of coffee consumed per day and the proportion of cells with aberrations. This association was independent of the effects of smoking and red cell folate level. These data suggest that smoking history, coffee consumption, and red cell folate level are important considerations for the design and interpretation of fragile site studies in cancer cytogenetics.

Increased sister chromatid exchange associated with smoking and coffee consumption.

Sister chromatid exchange (SCE) is a very sensitive cytogenetic assay for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to be exposed to such agents. We have, however, relatively little knowledge about common lifestyle factors that may influence SCE and therefore complicate any study designed to examine the effects of exposure to genotoxins. In this study, we assessed the effect of cigarette smoking and coffee consumption on SCE. Smoking was associated with an increase of approximately 2 SCEs per cell and a decrease in cell proliferation. A positive linear relationship between SCE and coffee consumption was also observed. This effect was similar for smokers and nonsmokers. Additionally, the folic acid content of cell culture medium seemed to affect neither SCE nor cell proliferation.

Folate- and deoxyuridine-sensitive chromatid breakage may result from DNA repair during G2.

A substantial increase in chromosome breakage was seen in proliferating human lymphocytes treated with 1-beta-D-arabinofuranosyl cytosine (cytosine arabinoside, cytarabine, araC) during the last 2 h of culture. The increase was larger in low folate media than in high folate media and larger still in low folate media supplemented by deoxyuridine. Similar results were found when cells were exposed to aphidicolin for the last 2 h of culture. The results provide additional evidence that folate-sensitive chromosome breakage is a consequence of abnormal DNA synthesis (in particular incorporation of deoxyuridine) and subsequent attempts during G2 to repair the abnormal DNA.