PMID- 9820661
OWN - NLM
STAT- MEDLINE
DCOM- 19981201
LR  - 20190819
IS  - 0378-4274 (Print)
IS  - 0378-4274 (Linking)
VI  - 96-97
DP  - 1998 Aug
TI  - Analysis of chromosomal alterations induced by asbestos and ceramic fibers.
PG  - 155-62
AB  - Asbestos and other mineral fibers have long been known as carcinogenic agents. 
      However, the primary mechanisms of fiber-induced carcinogenesis still remain 
      unclear. We have investigated mitotic disturbances caused by amosite, 
      crocidolite, and chrysotile in Syrian hamster embryo (SHE) fibroblasts. We also 
      analyzed micronucleus formation as a result of mitotic disturbances, and carried 
      out a characterization of the induced micronucleus population by kinetochore 
      staining. In addition, the spindle fiber morphology was examined. Supravital 
      UV-microscopy was used to analyze changes in chromatin structure, impaired 
      chromatid separation and blocked cytokinesis. All three fiber types induced 
      micronuclei in SHE cells with a high frequency (up to 200 MN/2000 cells; dose 
      range: 0.1-5.0 microg/cm2) in a dose-dependent manner with a maximum between 48 
      and 66 h. Kinetochore staining revealed that 48% of fiber-induced micronuclei 
      reacted positively. Furthermore, spindle deformation was observed in cells with 
      disturbed meta- and anaphases while the spindle fiber morphology appeared 
      unchanged. Our results show that asbestos fibers may cause both loss as well as 
      breakage of chromosomes in the absence of direct interaction with spindle fibers. 
      In addition, we analyzed the induction of micronuclei, hyperdiploidy and 
      chromosome breakage in human amniotic fluid cells (AFC) in vitro by amosite, 
      chrysotile and crocidolite asbestos and ceramic fibers. The response of human 
      (AFC) and rodent (SHE) cells to fiber treatment was compared using the 
      micronucleus assay. AFC were much less susceptible than SHE cells to the 
      induction of micronuclei by mineral fibers. The application of fluorescence in 
      situ hybridization (FISH) with tandem DNA probes yielded more detailed 
      informations about specific structural chromosome aberrations in the 1(cen-q12) 
      and 9(cen-q12) regions and about abnormal numbers of chromosomes in interphase 
      AFC. Using this FISH approach we found a statistically significant increase of 
      chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 
      and 9 in AFC after exposure to asbestos and ceramic fibers. The number of 
      hyperdiploid cells was also significantly increased. These results show that 
      asbestos as well as ceramic fibers are inducers of structural and numerical 
      chromosomal alterations.
FAU - Dopp, E
AU  - Dopp E
AD  - Institute of Animal Physiology, Department of Biology, University of Rostock, 
      Germany.
FAU - Schiffmann, D
AU  - Schiffmann D
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Carcinogens)
RN  - 1332-21-4 (Asbestos)
SB  - IM
MH  - Amniotic Fluid/cytology
MH  - Animals
MH  - Asbestos/chemistry/*toxicity
MH  - Carcinogens/chemistry/*toxicity
MH  - Ceramics/*toxicity
MH  - *Chromosome Aberrations
MH  - Cricetinae
MH  - Dose-Response Relationship, Drug
MH  - Fibroblasts/drug effects/ultrastructure
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mesocricetus
MH  - Micronuclei, Chromosome-Defective/drug effects
MH  - Microscopy, Ultraviolet
EDAT- 1998/11/20 00:00
MHDA- 1998/11/20 00:01
CRDT- 1998/11/20 00:00
PHST- 1998/11/20 00:00 [pubmed]
PHST- 1998/11/20 00:01 [medline]
PHST- 1998/11/20 00:00 [entrez]
AID - S0378-4274(98)00063-0 [pii]
AID - 10.1016/s0378-4274(98)00063-0 [doi]
PST - ppublish
SO  - Toxicol Lett. 1998 Aug;96-97:155-62. doi: 10.1016/s0378-4274(98)00063-0.