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Occupational and environmental mutagenesis: validation and application of the HPRT in vivo mutation assay for risk assessment in humans

Objective

- To harmonize present methods and to work out statistical procedures for the analysis of mutation at the X-linked gene for hypoxanthine phosphoribosyltransferase (HPRT) in human and animal cells in vivo and in vitro

- To establish a data base for HPRT mutation allowing the comparisons of population data obtained in different countries, and mutational spectra obtained by various environmental chemicals and radiation in vitro

- To study occupational, environmental and life style factors affecting the HPRT mutant frequency in human populations, and to con-elate mutant frequencies and mutational spectra at the HPRT locus with genetic polymorphisms affecting the individual metabolic activity

Humans are exposed to a variety of chemical and physical agents with potential reactivity towards the genetic material in the cells of the body. The long term adverse effects of such genotoxic exposures include mutagenesis and carcinogenesis. Prevention against these adverse effects requires identification and early detection of the causative factors and the genetic alterations they impose.

Modern cell and molecular biology techniques allow the detailed analysis of mutation
frequency and mutational spectra at the HPRT locus in human and animal cells in vivo and in vitro. The entire HPRT gene has been sequenced, and it is therefore possible to use molecular genetic technology to identify all types of mutations occurring at the HPRT locus, and to establish mutational spectra.

The participating laboratories are specialists in various aspects of measuring and
characterizing genetic change at the HPRT locus in human and animal cells. Data
generated in these laboratories will form the basis for a HPRT mutation data base. To
ensure that data are comparable on a methodological basis, common protocols will be
worked out, and experimental methods and statistical procedures will be harmonized.
These objectives will be realized by the establishment of network procedures for
collection and evaluation of data and distribution of information between partners. Such procedures will be worked out during frequent meetings and workshops, as well as through the exchange of scientific personnel between the laboratories. Literature surveys will be carried out to incorporate data from non-participating laboratories.
The project is expected to facilitate an improvement in genetic risk assessment and the
understanding of the ætiology of occupation and environmental-related diseases.
Ultimately, such understanding will provide a clear rationale for preventive actions.

Funding Scheme

CON - Coordination of research actions

Coordinator

Karolinska Institute
Address
7,Haelsovaegen
141 57 Huddinge
Sweden