摘要:

The validity of the micronucleus test as a biomarker of chromosome damage in dividing mammalian cells is well established. This assay was used to study the response of peripheral lymphocytes of a 34‐yr‐old male patient following treatment with131l ablative radiation therapy following a total thyroidectomy. Coincidentally, 8 mo before diagnosis, the patient had provided a blood sample for an in vitro study of micronucleus induction following exposure to graded doses of x‐rays. The background frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while mean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells were observed following x‐ray doses of 5, 10, 15, 20, and 25 cGy, respectively. These data fit a nonthreshold, linear dose‐response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x‐ray study, the subject was diagnosed with thyroid cancer. Surgery was performed, and 5 wk later the patient received 1.78 GBq (48 mCi) of131l as adjuvant radiation therapy. Blood was drawn 11 d after the radiation treatment and at monthly intervals thereafter to analyze the frequency and persistence of micronuclei. The first posttreatment sample showed 35.5 micronuclei per 1000 binucleate cells. Based on the linear dose‐response equation from the earlier study, the sixfold increase in micronucleus frequency suggests a dose to the peripheral blood of approximately 11 cGy. The cytogenetic dose estimate compares to ∼30 cGy using a new model based on external whole‐body counting data. Nine consecutive monthly samples have been analyzed to date. Although the micronucleus count has fluctuated (four‐ to sixfold above background), the frequency after 8 mo is equivalent to the first posttreatment sample. Data show that radiation‐induced cellular lesions persist for months following relatively brief radiation exposure to a medical isotope. Results of this study support the conclusion that the lymphocyte micronucleus test is a rapid, sensitive, and perhaps quantitative biomarker of low‐dose (<25 cGy) radiation exposure.

ISSN:0098-4108    

DOI:10.1080/15287399309531802

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Three biomarkers for benzene exposure were developed. The first biomarker, muconic acid in urine, results from the ring opening of a benzene metabolite. A gas chromatography/mass spectroscopy (GC/MS) assay was developed to measure urinary muconic acid, and the analyte in urine samples from workers occupationally exposed to benzene was determined. Workers exposed to benzene concentrations as low as 4.4 ppm over an 8‐h day showed higher urinary muconic acid concentrations than did any control individual (p < .005). The second biomarker,S‐phenylcysteine (SPC) in hemoglobin (Hb), results from the addition of benzene oxide to a cysteine sulfhydryl group. A GC/MS assay was developed to measure SPC in the blood of F344/N rats and B6C3F, mice exposed to benzene by inhalation. The cysteine moiety on rat Hb is at a more accessible site than on Hb of mice or humans, and rats showed considerably higher levels of SPC than did mice. As yet, we have been unable to detect SPC in the globin of humans occupationally exposed to benzene. The third biomarker is SPC in albumin. In humans occupationally exposed to average concentrations of 0, 4.4, 8.4, and 23.1 ppm benzene, 8 h/d, 5 d/wk, SPC increased in the exposed groups linearly, giving a statistically significant slope (p < .001) of 0.044 ± 0.008 pmol/mg albumin/ppm. The assay for SPC is arduous and often imprecise; assuming these difficulties can be overcome, muconic acid in urine and SPC in albumin may be useful for accurately determining benzene exposure.

ISSN:0098-4108    

DOI:10.1080/15287399309531803

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531804

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531805

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Living organisms are continuously exposed to reactive oxygen species as a consequence of biochemical reactions as well as external factors. Oxidative DNA damage has been implicated in aging, carcinogenesis and other degenerative diseases. The urinary excretion of the DNA repair product 8‐hydroxydeoxyguanosine (8OHdG) has been proposed as a noninvasive biomarker of oxidative DNA damage in humans in vivo. We have developed a three‐dimensional HPLC analysis with electrochemical detection for the analysis of 8OHdG in urine and studied factors affecting the excretion of this biomarker in 83 healthy humans and in various laboratory animals, including dog, pig, and rat. Previously, other groups have used comparable HPLC methods or gas chromatography‐mass spectrometry with selective ion monitoring for measuring the excretion of 8OHdG in humans, rats, mice, and monkeys. In the 169 humans studied so far, the average 8OHdG excretion was 200–300 pmol/kg per 24 h with a sevenfold range, and the coefficient of variation was 30–40%. This excretion corresponds 140–200 oxidative modification of guanine bases per cell per day. Thirty‐two smokers from our study population excreted 50% (31–69%; 95% confidence interval) more 8OHdG than 53 nonsmokers. This indicates a 50% increased rate of oxidative DNA damage from smoking, adding to the other well‐known health hazards of smoking. The biochemical‐physiological basis is unknown but may be related to smoke constituents including or generating reactive oxygen species and/or consuming antioxidants and/or the well‐known enhancing effect of smoking on the metabolic rate. In our 83 healthy subjects the 8OHdG excretion correlated with body composition. Thus, lean and/or male subjects excreted more than obese and/or female subjects, possibly related to differences in metabolic rate. In accordance, the excretion of 8OHdG decreased after calorie restriction, which will cause a decline in the metabolic rate. Across the investigated species, humans, dogs, pigs, and rats, the excretion of 8OHdG correlated with the specific metabolic rate, confirming data from other groups on humans, monkeys, rats, and mice. The excretion of 8OHdG decreased with age in rats in parallel with the decline in metabolic rate with advancing age. The excretion of 8OHdG reflects the formation and repair of only one out of approximately 20 described oxidative DNA modifications. So far, methods are not available for the determination of the corresponding repair products, except 8OHdG and thymidine glycol, in urine. Moreover, the importance in terms of mutagenicity, particularly regarding tumour supressor genes and oncogenes, is mainly documented for 8OHdG in DNA. In mammalian cells an excission repair enzyme complex for 8OHdG has been demonstrated, but whether the main product is 8OHdG or the base is yet unknown. In addition, 8OHdG may derive from DNA during turnover of mitochondria and cells as well as from oxidation in the deoxynucleotide and deoxynucleoside pools that provide building blocks for new DNA. Thus, the excretion of 8OHdG will reflect the general average risk of promutagenic oxidative adducts in DNA of all tissues and organs. We suggest that the individual variation in the apparent massive extent of oxidative DNA‐damage in humans predicts the rate of aging and the risk of cancer as well as other degenerative diseases. The use of 8OHdG and similar urinary biomarker of oxidative DNA damage offers a valuable tool for testing such hypotheses in humans.

ISSN:0098-4108    

DOI:10.1080/15287399309531806

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

A large part of the commercial flower production in Italy is located in the western part of the Liguria region, near the French border. The use of pesticides in this area has been much higher than the national average. The frequency of micronuclei in peripheral blood lymphocytes was evaluated in a group of 71 floriculturists working in this area and in a control group of 75 healthy blood donors living in the same area. A significant increase of micronucleated lymphocytes was observed in floriculturists as compared to unexposed subjects (8.57 vs. 6.67, p < .05). Females showed a marked increase in MN frequency (45% higher than males) independently of the exposure. A dose‐response relationship was observed between duration of exposure and MN frequency. The condition of exposure was also found to influence the micronuclei frequency. Increased relative risks in greenhouse workers (RR = 1.31) and in people working alternately in the greenhouse and in the open field (RR = 1.46) was observed with respect to the reference population.

ISSN:0098-4108    

DOI:10.1080/15287399309531807

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Communities surrounding the Rocky Mountain Arsenal (RMA), a Superfund site in Colorado, were studied in order to determine whether exposures to mercury were greater among persons who resided there than among residents of a comparison area 12–15 miles distant. From a census‐based stratified random sample, 469 persons were interviewed and urine samples were obtained for biomonitoring. Mercury was detected in urine from 32 (6.8%) of the 469 persons sample at a detection limit of 5 ppb. Trace levels of mercury (detectable, but nonquantifiable) were found in 80 (17.1 %) of the persons sampled. Neither the frequency of detection, the arithmetic mean, nor the geometric mean value for urine mercury was found to be statistically different when persons living near the site were compared to persons from the more distant comparison area. The risk of mercury exposure associated with demographic variables, residence, occupation, hobbies, dietary habits, water supply, housing, and activity patterns was evaluated. In the second stage of the evaluation, the Neurobehavioral Core Test Battery (NCTB) is being used to assess individual functional deficits and nervous system disorders associated with exposure to mercury and other neurotoxic chemicals.

ISSN:0098-4108    

DOI:10.1080/15287399309531808

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Hormone assays have been developed and applied for monitoring reproductive function using self‐collected urine samples in non‐clinical populations of women. Early pregnancy loss, menstrual dysfunction, reduced fertility as well as the site of toxicity can now be assessed using daily early morning urine samples. The understanding of the specific limitations of individual assay systems is important, however, to make the best use of these systems. The use of multiple end‐points and computer algorithms is suggested to avoid misclassification of adverse reproductive events.

ISSN:0098-4108    

DOI:10.1080/15287399309531809

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Despite years of research, the etiology of most birth defects remains largely unknown. Interview instruments have been the major tools in the search for environmental causes of birth defects. Because of respondents’ problems with recognition and recall, interviews are limited in their capacity to measure certain exposures. Laboratory scientists can have a major impact on defining markers of environmental exposure and genetic susceptibility. The Centers for Disease Control is starting a case‐control study of serious birth defects on the basis of a population‐based surveillance system for birth defects diagnosed during the first year of life in metropolitan Atlanta. Each year, 300 infants with selected birth defects (case subjects) and 100 population‐based control subjects (infants without birth defects) will be enrolled in an ongoing study that will supplement surveillance. In addition to conducting extensive maternal interviews, we will collect blood and urine specimens from case and control subjects and their mothers for laboratory testing. Eventually, some environmental sampling may be incorporated. Particular areas of emphasis are (1) nutritional factors, specifically measuring maternal folic acid levels and other micronutrients (e.g., zinc) to explore their role in the etiology of neural tube defects, (2) substance use, specifically measuring cocaine metabolites in the blood and urine to explore their role for specific vascular disruption defects, and (3) environmental factors such as pesticides and aflatoxins, to explore their potential relationships with specific defects. In addition, a DNA bank will be maintained to evaluate the role of specific candidate genes in the etiology of birth defects. The development and testing of these methods could be useful to assess the interaction between environmental exposures and genetic susceptibility in the etiology of birth defects.

ISSN:0098-4108    

DOI:10.1080/15287399309531810

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531811

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor