Research project ST/01 (Research action ST)
THEME.
Sensitivity of the different biomarkers to exposure and their causal relationship with two types of potential industrial mutagen/carcinogen: epoxide-forming carcinogens and cobalt-containing dust.
Theme of the secondary study:
Relevance of the SCGE to the evaluation of genotoxicity in biomonitoring studies.
OBJECTIVES.
Objectives of the network:
The study will attempt to establish a relationship between the level of exposure (internal and external) to two types of potentially genotoxic agent (epoxides and cobalt-containing dust), the relationship between these agents and that between the detected genotoxic effects. The most effective markers of genotoxic effects will be selected during a preliminary experimental stage. In the next stage, the selected markers will be examined by means of an epidemiological study. The objective will be to discover, if possible, exposure levels that do not induce genotoxic effects. This data should assist in the formulation of exposure standards for the agents in question. The principal objective is the primary prevention of work-related cancers.
ST/01/001:
Identification and validation of haemoglobin and DNA adducts as parameters in the biomonitoring of workers exposed to epoxide-forming carcinogens.
Objectives of the personal contributions:
- Further development and validation of the haemoglobin and DNA adduct detection method. The developed techniques will be applied in the form of a field study.
- Comparative research into the kinetics of haemoglobin and DNA adduct formation. The relationship between adduct formation and the manifestation of cytogenetic effects will be studied.
- Research into interindividual variations in enzymatic activity in the metabolism of epoxides.
- Research into parallels between the metabolism of different epoxides.
ST/01/002:
Experimental and clinical epidemiological research into the carcinogenic potential of cobalt compounds.
Objectives of the personal contributions:
- Experimental research in vitro: The effects of cobalt and cobalt compounds on epithelial alveolar cells in humans and animals will be examined in terms of (1) cellular dysfunction and damage caused by oxidative mechanisms, and (2) genotoxicity. These two factors are relevant to lung
cancer.
- Clinical epidemiological study: to ascertain whether patients with lung complaints (fibrosis) arising from workplace exposure show evidence of
cytogenetic damage. The results will be compared with those obtained from comparable patients suffering from pulmonary fibrosis that was not caused by exposure to cobalt (to ascertain the specific carcinogenicity, if any, of cobalt) and from workers in good health, whether or not exposed to cobalt.
ST/03/008:
Identification of (cyto)genetic changes caused by workplace exposure to epoxide-forming carcinogens or cobalt: experimental and clinical epidemiological study.
Objectives of the personal contributions:
(a) epoxide-forming carcinogens
A variety of points need to be studied in order to evaluate the relative genotoxicity of epoxide- forming carcinogens. Our contribution will centre on the detection of DNA-rupturing capacity compared to SCE (ULg) and adducts (ULg and KUL).
(b) Hard metals containing cobalt and its alloys
Experimental and epidemiological observations relating to lung cancer suggest that acceptable limits for cobalt exposure will depend on the exposure conditions (with or without carbides). In order to define these limits, the following questions will be answered on a step-by-step basis:
- Do cobalt and its alloys have a genotoxic effect on lymphocytes as reporter cells for biomonitoring purposes and on lung cell lines as target
cells for lung tumours?
- Do these genotoxic effects have a direct impact on DNA or via interference with recovery systems?
- What are the most genotoxic combinations?
- Are the genotoxic effects detected in the event of human in vivo exposure?
Objectives of the secondary study:
To obtain a better understanding of the relationship between DNA ruptures and chromosome alterations induced by a known carcinogen (ethylene oxide) and a less fixed mutagen (cobalt). This effect will be examined using the Single Cell Gel Electrophoresis technique (SCGE), which will be tested at the same time for its sensitivity and application in biomonitoring studies.
ST/10/014:
Experimental and epidemiological study into the genotoxic potential of inhaled particles containing cobalt dust.
Objectives of the personal contributions:
The genotoxic potential of particles of metallic cobalt and hard metals will be compared by means of two complementary approaches:
- experimental, by studying DNA damage caused by these particles;
- through a clinical epidemiological study, by evaluating the level of exposure to cobalt amongst groups of workers exposed to these particles.
ST/12/010:
Evaluation of damage to human genetic material induced by different epoxides, using cytogenetic and molecular bio-indicators.
Objectives of personal contributions:
To make available to the network the developed and validated molecular and cytogenetic technological expertise to ascertain and/or quantify the effects induced by workplace exposure to epoxides. This expertise includes:
- Study of frequency variations in the exchange of sister chromatids (SCEs) and the kinetics of appearance (and disappearance) of SCE high frequency cells (HFCs).
- Study of stable chromosomal anomalies using recent technology: whole chromosome painting.
- The cellular proliferation index (PRI) will be analysed. Recently obtained personal results suggest clonal selection in cellular cultures from
subjects who have experienced workplace exposure to genotoxic agents.
- Study of DNA adducts: the different adducts obtained will be analysed in G.C./M.S. after derivation and isotope marking (C13 and C14 to identify all formed adducts properly and to avoid missing any adducts which might, for instance, adhere strongly to the chromatography column).
Identificatie en validatie van gevoelige merkers voor de biomonitoring van werknemers blootgesteld aan potentiële mutagenen/carcinogenen. Toepassing voor arbeiders blootgesteld aan epoxide-vormende carcinogenen en kobalt-bevattende stof: eindverslag 1994-1998
Kirsch-Volders, M. - Laurent, Ch. - Lison, D. ... et al Brussel: DWTC, 1999 (SP0939)
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Identification and validation of sensitive markers for the biomonitoring of workers occupationally exposed to potential mutagens/carcinogens. Application to workers exposed to epoxide-producing carcinogens and cobalt-containing dust: executive summary
Brussels: OSTC, 1999 (SP0941)
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