Inhibitory
effects of herbal teas and herb extracts on the mutagenicity of 1-methyl-1,
2, 3, 4-tetrahydro- β -carboline-
3-carboxylic
acid upon treatment with nitrite in the presence of ethanol
Minoru Higashimoto, Yoshinobu Akada, Masao Sato, Yoshihide
Yamada, Tomomi Kuwahara and
Yoshinari Ohnishi …………………………………………………………………………………………………1
第29 回大会受賞講演
学術賞 JEMS Award 2000
Establishment
of regulatory sciences in the field of mutagenesis research
Toshio Sofuni
変異原研究領域におけるレギュラトリーサイエンスの確立
祖父尼俊雄…………………………………………………………………………………………………………9
研究奨励賞 JEMS Achievement Award 2000
Recombinational
DNA repair and maintenance of genomic integrity mediated by p53
Masamitsu Honma
がん抑制遺伝子p53 の組換え修復を介した遺伝的安定化機構
本間正充……………………………………………………………………………………………………………15
Mechanisms
for the oxidative stress response and oxidative mutagenesis in Escherichia
coli
Tatsuo Nunoshiba
大腸菌の活性酸素防御応答と突然変異誘発機構に関する研究
布柴達男……………………………………………………………………………………………………………23
第29 回大会シンポジウム
Symposium, 29th JEMS annual meeting, 2000
レスポンダーとノンレスポンダー；遺伝的多型と環境変異原研究
Responders and nonresponders ；Genetic polymorphism and environmental
mutagen research
Effects
of polymorphism in drug-metabolizing enzymes in the mutagenic activation
of chemicals
Tetsuya Kamataki, Ken-ichi Fujita, Hirotaka Kushida, Yuri Umetsu,
Masami Miyamoto, Noritaka Ariyoshi
薬物代謝酵素の遺伝的多型の変異原活性化における意義
鎌滝哲也，藤田健一，串田浩孝，梅津有理，宮本昌美，有吉範高…………………………………………33
今，私の考える環境変異原研究とは；21 世紀に向けて
My consideration on environmental mutagen research ：Perspectives
for the 21st century
My
consideration on environmental mutagen research ：Perspectives for the
21st century
Yu F. Sasaki and Toshio Sofuni
今，私の考える環境変異原研究とは；21 世紀に向けて
佐々木 有，祖父尼俊雄……………………………………………………………………………………………39
付録
Committee on Mutagenicity of Chemicals in Food, Consumer Products and
the Environment （COM ）
Guidance on a Strategy for Testing of Chemicals for Mutagenicity …………………………………………………45
Original Article
Inhibitory
effects of herbal teas and herb extracts on the mutagenicity of 1-methyl-1,
2, 3, 4-tetrahydro- β -carboline-
3-carboxylic acid upon treatment with nitrite in the presence of ethanol
Minoru Higashimoto, Yoshinobu Akada, Masao Sato, Yoshihide Yamada,
Tomomi Kuwahara and Yoshinari Ohnishi
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima
770-8514, Japan,
Yamada Yakken Co., Ltd., Osaka 577-0948, Japan,
School of Medicine, The University of Tokushima, Tokushima 770 - 8503,
Japan
Summary
The mutagenicity of 1-methyl-1, 2, 3, 4-tetrahydro- β -carboline-3-carboxylic
acid （MTCCA ）, a
major mutagen precursor in soy sauce, upon treatment with nitrite and
ethanol was considerably
reduced by the addition of herbal tea or herb extracts in the reaction
mixture when it was treated
with 50 mM nitrite at pH 3, 37 ℃for 60 min in the presence of 7.5
％ethanol. Among the herbal teas
tested, Banaba and Tencha teas showed strong mutagenicity-reducing
activity, and Kakinoha,
Kakidooshi and Yomogi teas, and Tochu and Senna teas also showed moderate
and weak
antimutagenicity, respectively, in the Ames Salmonella mutagenicity
test. Abundant amounts of
typical polyphenols such as catechins were detected in the highly antimutagenic
herbal teas. The
antimutagenicity and the reducing power of herbal teas were positively
correlated. Among the herb
extracts tested, Jiou extract showed strong antimutagenicity and Touki
extract was mildly
antimutagenic. Oubaku extract showed strong bactericidal activity because
of its high content of
alkaloid berberine. Diluted Oubaku extract showed dose-dependent antimutagenicity.
These results
suggest that the mutagenicity of MTCCA upon treatment with nitrite
in the presence of ethanol is
decreased by mixed fractions containing polyphenols such as catechins,
which have strong
reducing power, and other compounds such as derivatives of catechins,
which have little reducing
power.
Keywords ：antimutagenicity, herb, nitrosation, soy sauce, ethanol
Abbreviations ：MTCCA, 1-methyl-1, 2, 3, 4-tetrahydro- β -carboline-3-carboxylic
acid ；EC,
（−）-epicatechin ；ECG,（−）-epicatechin gallate ；EGC,（−）-epigallocatechin
；EGCG,
（−）-epigallocatechin gallate ；FIA, flow-injection analysis ；HPLC,
high-performance liquid
chromatography.
received ：September, 14, 2000 accepted ：February 14, 2000
Environmental Mutagen Society of Japan
研究奨励賞
JEMS Achievement Award 2000
がん抑制遺伝子p53 の組換え修復を介した遺伝的安定化機構
本間 正充
国立医薬品食品衛生研究所変異遺伝部 〒158-8501 東京都世田谷区上用賀1-18-1
Recombinational
DNA repair and maintenance of genomic integrity mediated by p53
Masamitsu Honma
National Institute of Health Sciences, Division of Genetics and Mutagenesis
1-81-1 Kamiyoga, Setagaya-ku, Tokyo 158 - 8501, Japan
Summary
Chromosomal double strand breaks （DSB ）occurring in mammalian cells
can initiate genomic instability
and their misrepairs result in chromosomal deletion, amplification,
or translocation, common findings in
human tumors. The tumor suppressor protein p53 is involved in maintaining
genomic stability. We
demonstrate here that the deficiency of wild-type p53 protein may allow
unrepaired DSB to initiate
chromosomal instability. The human lymphoblastoid cell line TK6-E6
was established by transfection with
HPV16 E6 cDNA into parental TK6 cells via a retroviral vector. Abrogation
of p53 function by E6 resulted in
an increase in the spontaneous mutation frequencies at the heterozygous
thymidine kinase （tk ）locus.
Almost all TK-deficient mutants from TK6-E6 cells exhibited loss of
heterozygosity （LOH ）with the
hemizygous tk allele. LOH analysis with microsatellite loci spanning
the long arm of chromosome 17, which
harbors the tk locus, revealed that LOH extended over half of 17q toward
the terminal end. Cytogenetic
analysis of LOH mutants by chromosome painting indicated a mosaic of
chromosomal aberrations involving
chromosome 17, in which partial chromosome deletions, amplifications
and multiple translocations appeared
heterogeneously in a single mutant. We speculate that spontaneous DSB
triggers the breakage-fusion-bridge
cycle leading to such multiple chromosome aberrations. In contrast,
no chromosomal alterations
were observed in TK-deficient mutants from TK6-20C cells expressing
wild-type p53. In wild-type p53 cells,
spontaneous DSB appear to be promptly repaired through recombination
between homologous
chromosomes. These results support a model in which p53 protein contributes
to the maintenance of
genomic integrity through recombinational repair.
Keywords ：p53, genomic instability, double-strand break （DSB ）,
recombinational DNA repair, loss of
heterozygosity （LOH ）
受付：2001 年4 月25 日 受理：2001 年5 月7 日
日本環境変異原学会
本稿は日本環境変異原学会第29 回大会において発表された2000 年度研究奨励賞受賞講演である.
This paper is the lecture of the JEMS Achievement Award （2000 ）presented
at the 29th JEMS annual meeting, 2000.
大腸菌の活性酸素防御応答と突然変異誘発機構に関する研究
布柴 達男
東北大学大学院生命科学研究科分子生命科学専攻遺伝子システム学講座
〒989-8578 仙台市青葉区荒巻字青葉
Mechanisms
for the oxidative stress response and oxidative mutagenesis in Escherichia
coli
Tatsuo Nunoshiba
Institute of Biomolecular Science, Graduate School of Life Science,
Tohoku University,
Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi 989 - 8578, Japan
Summary
Bacterial cells employ transcriptional factors which sense elevated
levels of oxidative stress and regulate
expression of antioxidant genes. In E. coli, two redox-responsive transcriptional
regulators, SoxR and OxyR,
have been well characterized. The SoxR contains iron-sulfur centers
to sense superoxide stress or nitric
oxide. The OxyR contains a thiol-sulfide redox-switch to sense peroxide
stress. In this review, I present
discussion about the source of oxidative stress in bacteria, oxidative
lesions of cellular bio-molecules, the
antioxidant responses and their regulation mechanisms.
Keywords ：OxyR ，SoxR ，disulfide bond ，iron-sulfur cluster ，transcriptional
activator
受付：2001 年5 月9 日 受理：2001 年5 月24 日
日本環境変異原学会
本稿は日本環境変異原学会第29 回大会において発表された2000 年度研究奨励賞受賞講演である.
This paper is the lecture of the JEMS Achievement Award （2000 ）presented
at the 29th JEMS annual meeting, 2000.
今，私の考える環境変異原研究とは；21 世紀に向けて
佐々木 有 ，祖父尼 俊雄
1八戸工業高等専門学校 〒039-1192 青森県八戸市田面木上野平16-1
2オリンパス光学工業（株），LRC 〒192-8512 東京都八王子市久保山町2-3
My
consideration on environmental mutagen research ：Perspectives for the
21st century
Yu F. Sasaki and Toshio Sofuni
Hachinohe National College of Technology, Tamonoki Uwanotai 16-1, Hachinohe,
Aomori 039-1192, Japan
LRC, Olympus Optical Co. Ltd., 2-3 Kuboyama-cho, Hachioji-shi, Tokyo
192-8512, Japan
Summary
This is a report of the Symposium entitled “My consideration on environmental
mutagen research ：
Perspectives for the 21st century ”which was held at the 29th Annual
Meeting of the Japanese
Environmental Mutagen Society on November 16, 2000 in Sendai. Six speakers
from different institutes
such as University （Professor Hayatsu ）, National Institute （Drs
Wakabayashi, Hayashi and Nohmi ）,
Contact Laboratory （Dr. Tanaka ）and Pharmaceutical Laboratory （Dr.
Shimada ）presented their opinions
on environmental mutagen researches, activites, and especially their
perspectives on this research field for
the 21st century. The issues presented by these speakers address essential
components for establishment of
a strategy of environmental mutagen research in to the 21st century.
Keywords ：environmental mutagen research, perspective, 21st century
受付：2001 年4 月27 日 受理：2001 年5 月7 日
本稿は日本環境変異原学会第29 回大会シンポジウム II「今，私の考える環境変異原研究とは；21
世紀に向けて」で発表された.
This paper was presented to the symposium II“My consideration on environmental
mutagen research ：Perspectives for the 21st century ”
at the 29th JEMS annual meeting, 2000.