Environmental and Molecular Mutagenesis - Legacy Tobacco ...

536 r
THE COLLABORATIVE STUDY ON MOUSE SPOT TEST IN JAPAN .
x .TUtikawa, T .Shibuya, S .}litotsumachi, T .Ohshima and A . Wakata, The Collaborative Study
Group for the Mouse pot Test, Hadano, Kanagawa 257 (JAPAN)
The collaborative study on mouse spot test (MST) was carried out in 11 different
laboratory in Japan . Mouse strain used in this study were male PW (established by
Tutikawa and Harada) and six different females ; C57BL/6 (B6), four 810 congenic lines
(B10, B10A, B10BR and BlOD2) and KYG . The test campound employed was N-ethyl-N-nitrosourea
(ENU) . ENU was dissolved in phosphate buffer (pH 6 .0) and intraperitoneally
treated to female mice at dag_10 .5 of pregnancy . The observations on the F1 mice were
done on the following characterst recessive color spots (RS), white midventral spots
(WMVS), misdifferentiation spots (MDS) and external malformations at their weaning
period .
The incidence of RS lineally increased as dose of ENU in all matings . These results
were clearly different from that of mouse specific locus test (Russell et al,
1982) . These observations may suggest that repair capacity is deficient in melanoblast
cells in mouse embryos . In the case of KYG, the incidence of RS induced by ENU
was always higher than that in the other matings .
The fertility rate in plug-proved females was extremely low in 86 females that the
other females mated .
From these results, we recommend to use male PW and female 810 on MST in Japan .
537
N-ETHYL-N-NITROSOUREA INDUCED RECESSIVE MUTATIONS IN MOUSE PRIMORDIAL GERM CELLS .
T .Shibuya, N .Horiya, H .Matsuda, T .Hara, M .Ratoh and T .Murota, Hatano Research Institute
Food and Drug Safety Center, Hadano, Kanagawa, and Mitsubishi Kasei Co, Yokohama(JAPAN)
Previously we found that N-ethyl-N-nitrosourea (ENU) induced recessive mutation in
somatic cells and killed primordial germ cells (PGC) in mouse embryos (Shibuga at al,
1982) . We therefore carried out a specific locus test (SLT) on mouse PGC with ENU .
Male and female C3H/He mice were mated and pregnant females obtained were treated
with 30 or 50 mg/kg ENU at day 10 .5 of pregnancy . The F1 male mice obtained were mated
with tester female PW mice after they were grown . The obtained mice of the next qeneration
were checked for their coat•color and ear shape to evaluate whether or not PGC
had been mutated by ENU . The fertility of male mice was 99% and 38% at 30 or 50 mg/kg
ENU, respectively, much higher than the value in female mice .
Three mutants were obtained in the 30 mg/kg group fram 5,823 offspring, and the two
of them were recovered fram the same male, showing cluster mutations . Fifteen mutants
were gained from 2,837 offspring in the 50 mg/kg group, and most of those had originated
from cluster mutations . All mutants thus obtained are viable under hanozygous
conditions . The high viability of mutant genes under homozygous condition is similar
to that of an examination of the effect of ENU on stem-cell spermatogonia .
SLT in mouse PGC at different developmental stages (8 .5 and 13 .5 day of development)
by ENU are now in progress . Until now, mutants are obtained fram both experiments .
It may be concluded that early stage of PGC is a sensitive stage to ENU in mice .
538
GENOTOXICITY OF BENZENE AND ITS METABOLITES
H . Shimada, S . Itoh and S . Takayama
Research Institute of Daiichi Seiyaku Co ., Ltd ., Tokyo (JAPAN)
Benzene is known to have clastogenicity and myelotoxicity in animals, though which
metabolites cause these damages remain unclear . We investigated the relationships
between DNA single-strand breaks (SSBs) and ∎icronuclei formation induced benzene and
its metabolites in vivo and in vitro . Male ddY strain ∎ice were singly administered po
with benzene and killed at 12 to 72 h later . It was found that the SSBs in the bone
marrow cells was markedly increased at 36 h, and the ∎icronuclei frequency was markedly
increased at 42 h after the administration . In the ∎icronucleus test of the bensene
metabolites, phenol and hydroquinone induced ∎icronuclei but other metabolites (muconic
acid, hydroxyhydroquinone, 1 .4-benzoquinone, 2 .2'-biphenol . 4 .4'-biphenol and catechol)
did not . In vitro studies, hydroquinone, 1 .4-benzoquinone, 2 .2'-biphenol and hydroxyhydroquinone
induced SSBs in the bone marrow cells, while hydroquinone and 2,2'-
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 185
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