Current trends in the biological monitoring of exposure to carcinogens.

Vainio, Harri

doi:10.5271/sjweh.2260

Cited by 46 publications

(5 citation statements)

References 21 publications

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“…A number of techniques have been developed for monitoring human exposure to environmental or occupational carcinogens. Among these methods are the measurement of the chemical itself or its metabolites in body fluids (e.g., serum or urine) or the chemical bound to cellular macromolecules including DNA and protein, measurement of mutagens in urine, and measurement of the early biological effects, such as sister chromatid exchange and chromosomal aberrations (1). Although the analysis of biological samples can provide extremely valuable information on carcinogen exposure, human biomonitoring studies are limited by the availability of test material.…”

Section: Introductionmentioning

confidence: 99%

Immunologic methods for the detection of benzo[a]pyrene metabolites in urine

Gomes

Santella²

1990

Chem. Res. Toxicol.

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Two monoclonal antibodies (10C10 and 4D5) have been developed from the spleen cells of Balb/c mice immunized with 6-aminobenzo[a]pyrene covalently coupled to bovine serum albumin. These antibodies have been used in an immunoassay for the detection of benzo[a]pyrene and its metabolites in mouse urine. The antibodies were characterized in terms of sensitivity and specificity by competitive enzyme-linked immunosorbent assay (ELISA). With both antibodies, 50% inhibition of antibody binding is at 4 pmol of BP. The antibodies also cross-react with a number of BP metabolites as well as with several other polycyclic aromatic hydrocarbons (PAHs) including pyrene, 1-aminopyrene, and 7,12-dimethylbenz[a]anthracene but with different sensitivities. These results suggest that this assay will detect multiple PAH metabolites in urine. To test the assay on biological samples, mice were treated with [3H]BP, and urine was collected and digested with beta-glucuronidase and aryl sulfatase. Several methods were used to isolate BP and its metabolites from the urine, including ethyl acetate extraction, Sep-pak C18 cartridge chromatography, XAD2 resin chromatography, and immunoaffinity chromatography with antibody 4D5. Analysis of the urine extracts with antibody 4D5 gave 50% inhibition at 12-15 pmol of metabolites. Thus, quantitation of metabolites in this sample by competitive ELISA against a standard curve of BP would have underestimated actual metabolite levels by about 70%. This assay will be applied to the analysis of urines from individuals with environmental or occupational exposure. Since humans are usually exposed to BP in complex mixtures of PAHs, multiple metabolites may be present in the urine, making absolute quantitation difficult. This assay should thus serve as a general indicator of exposure to this class of chemicals.

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Section: Introductionmentioning

confidence: 99%

Immunologic methods for the detection of benzo[a]pyrene metabolites in urine

Gomes

Santella²

1990

Chem. Res. Toxicol.

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“…Increased MN was observed for patients administered many antineoplastic drugs [Osanto et al, 1990;Sarto et al, 19901. Circulating HPL endpoints (CA, SCE, and MN) have been used to detect genotoxic exposures [Vainio, 1985;Carrano, 1986;Brusick, 1987;Lucier and Thompson, 1987;Ashby, 1988;de Jong et al, 1988;Vennitt, 19881. emsa stain solution (Fucillo modification) was from EM Diagnostic Systems (Gibbstown, NJ). Phosphate buffer was prepared by adding 6.638 of KH,PO, and 3.26g of Na,HPO, to 1-L of distilled water and adjusting the pH to 6.5 with 2N HCI or 2N NaOH.…”

Section: Introductionmentioning

confidence: 99%

In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs

Boucher¹,

Livingston

Hee

1993

Environ and Mol Mutagen

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The aim of this study was to develop an in vitro human peripheral lymphocyte micronucleus bioassay involving phytohemagglutinin stimulant for urines containing adriamycin (ADR) and cyclophosphamide (CP). In vitro studies with defined concentrations of ADR, CP, and fresh urine showed that mitotic indices and micronuclei counts/1,000 cells had to be log (X + 1) transformed to be able to use parametric statistics and that a specific micronucleus assay for ADR in the presence of CP and urine for 5-15 ng ADR/mL had been developed. Whereas CP alone could be detected between 196-522 micrograms/mL, this effect was abolished in the presence of 15 ng ADR/mL. Interdonor variabilities relative to ADR sensitivity and CP linear dynamic range were marked, but intradonor variability was small. The MN bioassay tolerated < 10% urine. Results for urines from nine patients receiving antineoplastic drugs (CP, all; ADR, 3; 5-fluorouracil, 3; methotrexate, 3; vincristine, 4; procarbazine, 1; and megestrol acetate, 1) showed that only 1/3 patients given ADR were detected, and two others not given ADR were positive. All frozen urines from the 12 control subjects and the nine patients exhibited depressed mitotic index, with, however, no control patient urines inducing increased micronuclei. Two patients had urines of undefined genotoxic potential since undepressed mitotic indices were not attainable by dilution. The effects of combination chemotherapy in addition to freezing and storage influences were complex. More research is required to be able to interpret the results.

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“…The most common samples are peripheral blood, voided urine, and exhaled air. Depending on the target tissues, these samples will reflect with variable accuracy the biologically effective dose (33)(34)(35)(36). Reliable information on the relationship between biological indicator level in peripheral blood or urine and in the target tissue is highly desirable.…”

Section: Key Characteristics Expected Ofbiomarkers Ofexourementioning

confidence: 99%

The biological exposure indices: a key component in protecting workers from toxic chemicals.

Morgan

1997

Environ Health Perspect

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Biological monitoring of exposure to chemicals in the workplace is an important component of exposure assessment and prevention of adverse health effects. It should be employed in conjunction with ambient air monitoring to provide information on the absorbed dose of a chemical agent and the effect of all routes of exposure. Judgments regarding the acceptable level of a chemical or its metabolite in biological samples are facilitated by comparison to a reference value. The American Conference of Governmental Industrial Hygienists has established a series of recommended reference values called the Biological Exposure Indices (BEI). The history and characteristics of the BEI are reviewed, and their suitability for use by occupational health specialists is examined. A number of challenges and stimuli to the continued development and improvement of these reference values are described, and the impact of recent advances in macromolecular biology is assessed.

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Current trends in the biological monitoring of exposure to carcinogens.

Cited by 46 publications

References 21 publications

Immunologic methods for the detection of benzo[a]pyrene metabolites in urine

Immunologic methods for the detection of benzo[a]pyrene metabolites in urine

In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs

The biological exposure indices: a key component in protecting workers from toxic chemicals.

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