The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals

Premature (early) centromere division (PCD, i.e., the separation of centromeres during the prometaphase/metaphase of the mitotic cycle) seems to be a possible manifestation of chromosome instability in human chromosome-breakage syndromes. Chromosome instability also frequently occurs in the peripheral blood lymphocytes (PBL) of humans occupationally exposed to clastogenic agents, and is considered an etiologic factor of neoplastic diseases. In order to investigate the importance of PCD in cancer risk assessment, we studied the frequency of PCDs in PBL of 400 Hungarian subjects. The various groups comprised 188 control donors and 212 subjects occupationally exposed to different genotoxic chemicals, such as acrylonitrile (ACN) and/or dimethylformamide (DMF), benzene, cytostatic drugs, ethylene oxide (ETO), mixed exposure in the rubber industry, mixed organic solvents including CCl4, hot oil-mist, bitumen, and polychlorinated biphenyls (PCB). Data were compared with chromosomal aberration frequencies determined in the same samples. PCD yields are significantly higher in populations exposed to mixed chemicals, crude oil and cytostatic drugs, compared with controls. PCDs involving more than three chromosomes are also more frequent in ETO- and oil mist-exposed groups than in the others. The results indicate that the induction of PCDs is neither incidental nor artificial. As a consequence, we suggest that PCD can be developed into a new, exposure-related cytogenetic biomarker for a more adequate occupational cancer risk assessment. A further, follow-up epidemiological and cytogenetic investigation of PCD is in progress.