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Biomedical subjects

J A Reidy

Publications and source records attributed to J A Reidy.

At least 19 recordsLinked to original sources
PubMed2000

Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS.

Because of the ubiquity of phthalates and their potential role in increasing risk for cancer and reproductive dysfunction, the need for human exposure assessment studies is urgent. In response to this need, we developed a high-throughput, robust, sensitive, accurate, and precise assay for simultaneous measurement of trace levels of eight phthalate metabolites in human urine by HPLC-MS/MS. Human urine samples were processed using enzymatic deconjugation of the glucuronides followed by solid-phase extraction. The eluate was concentrated, and the phthalate metabolites were chromatographically resolved by reversed-phase HPLC, detected by APCI-tandem mass spectrometry, and quantified by isotope dilution. This selective analytical method permits rapid detection (7.7 min total run time) of eight urinary metabolites of the most commonly used phthalates with detection limits in the low nanagram per milliliter range. Assay precision was improved by incorporating 13C4-labeled internal standards for each of the eight analytes, as well as a conjugated internal standard to monitor deconjugation efficiency. This selective, sensitive, and rapid method will help elucidate potential associations (if any) between human exposure to phthalates and adverse health effects.

Calibration↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the maintenance of genetic stability.

DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases.

Animals↗
PubMed1989

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.

Chromosome Aberrations↗
PubMed1989

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.

Ascorbic Acid↗
PubMed1989

Complete culture medium is better than low folate medium for detecting increased chromosome aberrations in smokers in 48-h lymphocyte cultures.

We compared chromosome breakage in parallel, 48-h lymphocyte cultures established from smokers and nonsmokers using minimal essential medium (MEM) and MEM without folate (MEM-FA). There was a statistically significant, higher frequency of aberrations for smokers than for nonsmokers in cells cultured in MEM, but not in those cultured in MEM-FA. Thus, these data support the recommendation of the World Health Organization (1985) that population monitoring studies for exposure assessment should not use a low folate medium.

Adult↗
PubMed1988

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.

Adult↗
PubMed1988

Effects of folate in culture medium on common fragile sites in lymphocyte chromosomes from normal and leukemic children.

The expression of common fragile sites at 69 bands was evaluated in 20 normal children and in 15 children with newly diagnosed acute leukemia using medium with folate (FA+) and without folate (FA-). As expected, the FA- medium significantly increased expression of aberrations in all study groups but the differences were larger for normal children than leukemic children. The major effect of the FA- medium was a generalized increase in aberration frequency over all sites rather than site-specific increases. A tendency toward clumping of aberrations within cells was exhibited in both media. Aberrations were seen at 81% (FA+) and 83% (FA-) of the 69 bands, with 4 sites - 3p14, 6p21, 9q13, and 17q23 - recorded in most of the study individuals. In addition, 12 sites not previously recorded as common or rare sites had significant levels of expression in at least one study group.

Acute Disease↗
PubMed1987

Deoxyuridine increases folate-sensitive fragile site expression in human lymphocytes.

Deoxyuridine (dU) increases chromosome breakage at folic acid (FA)-sensitive common fragile sites (mostly 3p14 and 16q23) in human lymphocytes. This dU-related increase can be suppressed by thymidine or FA. These results suggest that the mechanism of fragile site expression in low FA medium involves misincorporation of dU into DNA.

Chromosome Fragile Sites↗
PubMed1987

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.

Aphidicolin↗
PubMed1986

Folic acid and chromosome breakage. III. Types and frequencies of spontaneous chromosome aberrations in proliferating lymphocytes.

The types and frequencies of spontaneous chromosome aberrations were studied in human lymphocytes cultured for 96 h in minimal essential medium (MEM) or MEM without folic acid (MEM-FA). In both media, the most frequent aberrations were chromatid gaps, isochromatid gaps and chromatid breaks. Chromosome (isochromatid) breaks and dicentrics were seen less frequently. Neither of these less frequent aberrations was seen in 4000 cells from MEM, but both were seen in 4000 cells from MEM-FA.

Cells, Cultured↗
PubMed1986

Folic acid and chromosome breakage. IV. Variance estimates from longitudinal studies of normal individuals and their implications for sample size and power to detect differences between populations.

The frequency of chromosome aberrations was studied in minimal essential medium (MEM) with and without folic acid (FA) in lymphocytes of 4 normal individuals, each sampled 12 times over a 1-year period. The cells cultured without FA had significantly more breaks and gaps. In both media about 75% of aberrations were classified as gaps. Calculations based on variance estimates suggest that the use of medium without FA could enhance the statistical power to distinguish differences in proportions of chromosome breakage between groups in the same study.

Analysis of Variance↗