INDUCTION OF MICRONUCLEI, HYPERDIPLOIDY AND CHROMOSOMAL BREAKAGE AFFECTING THE CENTRIC PERICENTRIC REGIONS OF CHROMOSOME-1 AND CHROMOSOME-9IN HUMAN AMNIOTIC-FLUID CELLS AFTER TREATMENT WITH ASBESTOS AND CERAMIC FIBERS/

This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chry sotile and crocidolite asbestos, and ceramic fibers. The response of h uman (amniotic fluid cells) and rodent (Syrian hamster embryo fibrobla sts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous inve stigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268- 271). All types of mineral fibers caused a significant increase of mic ronucleated cells. The kinetochore analysis revealed that an three typ es of asbestos and ceramic fibers yielded similar effects. Approximate ly 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by min eral fibers. This again demonstrates that SHE cells are more susceptib le to chromosomal changes than human amniotic fluid cells. The applica tion of fluorescence in situ hybridization (FISH) with tandem DNA prob es yielded more detailed information about specific structural chromos ome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about a bnormal numbers of chromosomes in interphase human amniotic fluid cell s, Using this FISH approach we found a statistically significant incre ase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after expos ure to asbestos and ceramic fibers compared to control cells. The numb er of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of s tructural and numerical chromosomal aberrations in human amniotic flui d cells.