Cytostatic drugs and health risks for exposed personnel: Search for new biomarkers

The use of antiblastic drugs has opened lip new perspectives in improvement of therapy and life qualify for cancer patients. The widespread clinical a pplication of cytostatic drugs implies risks for. exposed hospital personne l, due to genotoxic and toxic-reproductive effects. Biological monitoring i s fundamental to identify individuals at risk but is limited by the long la tency of chronic effects, absence of unique cellular targets and low sensit ivity of available laboratory tests. The objective of this study was to inv estigate toxic mechanisms by a molecular biology approach, searching for bi omarkers potentially useful in monitoring programs. The proposed experiment al model consisted of cell line exposure to cyclophosphamide, an alkylating agent of wide clinical use. Cellular response has been investigated focusi ng on potential targets at RNA level, through reverse transcription polymer ase chain reaction (RT-PCR) and differential display analysis. We studied t he expression of several genes involved in differentiation, apoptosis and c hemoresistance: ets1, bax, bcl-2, bag-1, bcl-X, mdr1 and mrp. Specific patt erns of mRNA modulations were observed. Differential display analysis revea led candidate genes induced or repressed following exposure: their characte rization is bz progress. Besides improving the understanding of toxic mecha nisms, identification of modulated molecular targets opens up new perspecti ves in exposure risk assessment, biomonitoring and preventive strategies at occupational level.