Environmental and Molecular Mutagenesis - Legacy Tobacco ...

507
DIETHYLSTILBESTROL i(DES) INDUCES CHROMOSOME STICKINESS IN SYRIAN
HAMSTER (SHE) FIBROBLASTS .
R . Schnitzler, ' . Sch~ fmann and M . Metzler, Institute of Toxicology,
University of Wtlrzburg, Versbacher Str . 9, W . Germany
The genotoxic effects of estrogens are still a matter of debate . Existing
data suggest that numerical chromosome changes rather than gene
mutations are involved in estrogen induced neoplastic transformation . We
have shown previously that DES induces micronuclei (MN) in a nonsynchronized
cell population already after 1-2 hrs, whereas agents causing gene
mutations (i .e . .4-NQO)_iriduce MN formation not before 12-18 hrs . This
supports the hypothesis of a DES in3uced disturbance of the mitotic apparatus
. - We report here that DES induces chromosome stickiness during
early mitosis in SHE cells without measurable alterations of the mitotic
index . After 7 hrs of DES treatment (40 }tM) mitotic cells showed a spheric
aggregation of the chromosomes . The spindle apparatus was found to
be morphologically altered in comparison to control cells . In many cases
we observed single chromosomes separated from the chromosome aggregation
None of them was connected to the mitotic spindle apparatus . In addition
the centrioles were located on top of the aggregate and in some cells
only one centriole could be detected . - These findings suggest that DES
interacts with the protein matrix of mitotic chromosomes, presumably
topoisomerase II . This interaction and the observed disturbance of . the
spindle formation should result in numerical chromosomal aberrations and
therefore could be the main reason for the formation of DES induced MN .
508
REPEATABILITY OF SPONTANEOUS AND CHEMICALLY-INDUCED SISTER CHROMATID
EXCHANGE (SCE) ~4ND CHROMO$MAL BREAKAC (CB) IN UNRELATED INDIVI~UALS . S,
Schwartz , L . Lasher , S.S. Wasserman , and M.M . Cohen ~ . Divi~on of Human Genetics . Division of
Geographic Medicine, University of Maryland School of Medicine, Medical Biotechnology Center of the
Maryland Biotechnology Institute, Baltimore, Maryland 21201 .
It is well-established that considerable variability in the frequency of sister chromatid exchange (SCE) and
chromosomal breakage (CB) exists within and among populations. Lymphocyte cultures from 27 individuals
.e ere examined, on 2-3 occasions during a 6-month -2 year interval, for spontaneous and clast en-induced
SCEs and CB following exposure to mitomycin C (MMC), bleomycin (BLM), streptonigrin~SN) and 4n
itroquinoline- I -oxide (4NQO) . These experiments were performed to assess the reliability of single SCE and
C B observations in evaluating an individual's response to environmental exposure . Data analysis utilizing a twoway
nested analysis of covariance for each parameter (SCE or CB) yielded information concerning variability
among the individuals as well as among the different cultures of a givenberson . These data clearly demonstrate
that the interindividual variation of both spontaneous and induced SCEs and induced CB is significantly greater
than among the cultures of the same person (pc0.01). A similar difference was not found for spontaneous
chromosome breakage . For spontaneous SCEa. SN- and BLM-induced SCEa, spontaneous CB and 4NQOinduced
CB, variation among sampling dates was not significantly greater than the variation within cultures ;
Khile for MMC-and 4NQO-induced SCEs and MMC- . BLM-, and SN-induced CB, variation among sampling
dates was significantly greater thin within sampling dates (p