Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts
Notes MOUSE MODELS FOR UNDERSTARDING HUMAN DEVELOPNffirfAL ANOMALIES
Valderico N . Generoso
Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-8077 (USA)
191
Mutaganesis research in mice has a long tradition of addressing the problems of
human genetic risk and of enriching our knowledge of basic mammalian biology . In line
with this tradition, we are using mouse models in order to understand the origin and
pathogenesis of certain classes of human developmental anomalies . One such model
involves the study of the developmental defects that are caused by chemically induced
chromosomal rearrangements and imbalances . Of interest are the specific chromosomes
involved, the nature of breakpoints, the teiotic segregation that produces unbalanced
segregants that survive to late gestation, and the sequence of changes that are
observed in the pathogenesis of the defects . Another model involves the study of
developmental anomalies that are produced subsequent to exposure of zygotes to certain
mucagens . The fetal malformations produced in these studies are generally similar to
the majority of human malformations, for which the etiology is largely unknown . The
evidence suggests a genetic basis for the mouse fetal anomalies, but of a type that is
different from conventional gene mutations and ehromosome aberrations .
Research sponsored jointly by the National Toxicology Program under NIEHS Interagency
Agreement Y01-ES-20085 and the OHER, U .S . DOE under contract DE-AC05-840R21400 with the
Martin Marietta Energy Systems, Inc .
192
COMPARISON OF THE GENOTOXIC EFFECTS OF 1- AND 2- NITROPROPANE IN THE RAT
E . George, B . Burlinson and D .G . Gatehouse, Dept . Genetic and Reproductive Tox .,
Glaxo Group Res . Ltd ., Ware, Herts, England .
2-nitropropane is a potent rat liver carcinogen, whilst the 1-isomer is
non-carcinogenic in rodents . Although the 2-isomer induces UDS in the rat liver,
uniformly negative results have been obtained in the mouse micronucleus test . The
inability of the latter to discriminate between the carcinogenic and non-carcinogenic
isomers may reflect either species-specific genotoxicity in vivo ; an organospecific
effect of the 2-isomer or an end-point specific effect .
To determine which of these factors precluded detection of 2-nitropropane in the
mouse micronucleus test, studies were carried out in the rat in which micronucleus
induction (bone marrov and liver) and UDS induction (liver) were measured after oral
treatment with each compound . 2-nitropropane was found to induce UDS in rat liver,
whilat the 1-isomer was negative, thus confirming earlier studies using the
intraperitoneal route . In the bone-marrov micronucleus test, small increases were
obtained with individual animals, however group means fell within the historical
control range and the results were considered negative . In the liver micronucleus
test, 2-nitropropane induced a highly significant response . Therefore the negative
mouse micronucleus test results reported for 2-nitropropane were not due to species
specificity, or end-point specificity ; but instead were a reflection of the
organospecific genotoxicity of this compound in vivo . These data provide further
evidence that bone marrov assays are insufficient for the detection of all genotoxic
carcinogens in vivo, indicating the need for a second tissue, although the choice of
end-point may be of less critical importanae .
193
A CHROMOSOME STUDY OF 387 REFERRED CASES HITH VARII3D GENETIC DISORDERS .
M .A.Ghalib, G .S.Issac, A .Jyothy and O .S .Reddy, Institute of Genetics and Hospital
for Genetic Diseases, Osmania University, Begumpet, Hyderabad . A .P . (INDIA) .
This paper describes the result of chromosome study carried out on 387 cases
suspected of chromosomal abnormalities . They were referred during the period
from January 1987 to July 1988 to the Cytogenetics Division of the Institute of
Genetics and Hospital for Genetic Diseases from the various districts of the State
of Andhra Pradesh, India . They Include congenital anomalies (134), am biguous
external genitalia (29) . Down's syndrome (101) . Klinefelter's phenotype (17) .
Turner's phenotype (12), and primary and secondary amenorrhea (94) cases .
Out of these 387 cases . 119 were found to have chromosomal abnormalities, a
frequency of 30 .75% of abnormal karyotypes, leaving 268 with normal keryotypes .
Autosomal aberrations were detected in 99 cases and the remaining 19 cases had
sex-chromosome abnormalities . The frequency of 30 .75% in a referred population
for chromosomal aberrations is considered high when compared to similar reports
from other countries . Factors related to the parents that might have a predisposition
in the aetiology of the aneuploidies will be discussed . Acknowledgements .
The first author would like to thank the Rector . University of Aden, Government
of P .D .R . of Yemen and the Education Officer . Ministry of Human Resources Development
. Govt . of India fo~ financial support . The authors acknowledge the Director
of the Institute for providing facilities .
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