1997 Fiscal Year Annual Research Report

新人為起源有害物質の継世代的人体影響

Research Project

Project/Area Number	05278114
Research Institution	Osaka University
Principal Investigator	野村大成大阪大学, 医学部, 教授 (90089871)
Co-Investigator(Kenkyū-buntansha)	福岡正道昭和薬科大学, 薬学部, 教授 (10173329) 藤井儔子帝京大学, 医学部, 教授 (70075224) 高橋由明新潟大学, 医学部, 講師 (60115045) 嶋昭紘東京大学, 大学院・理学系研究科, 教授 (60011590) 中島裕夫大阪大学, 医学部, 助手 (20237275)
Keywords	新人為起源有害物質 / 継世代的影響 / 生殖器障害 / 形態異常 / 機能的異常 / 分子遺伝学的異常 / 子孫への伝達 / チェルノブイリ放射能汚染の遺伝的影響
Research Abstract	人類は、科学の進歩とともに、膨大な数の化学物質を地球上に造り出したことにより、人類の歴史上、これまで出くわしたことのない物質に曝露されることになった。本研究は、地球レベルでの情報収集と、最新の科学技術を用いて新人為起源有害物質の継世代的影響を総合的に研究し、人類の未来をうかがう研究成果の蓄積と継世代人体障害の防護を目的とする。本年度の成果は以下の通りである。 1)継世代的障害: ダイオキシン(TCDD)の雄又は雌マウスへの投与により、子孫(F_1)に有意に優性致死と重度の奇形が発生した。^<60>Coγ線の低線量率連続照射によっても有意には至っていないが、F_1に腫瘍の上昇が見られた。思春期雄ラットへの除草剤LinuronやGlyphosate投与によりF_1に薬理学的異常(Ca感受性の増大と副甲状腺ホルモン分泌の低下)が見られた。雄メダカへの、ダイオキシンの作用によってもF_1に胚早期死、眼球形成異常が有意に増加した。 2)生殖器障害の分子レベルの解析: フタル酸エステルによるラット精子死亡は、赤血球への障害を介して支持細胞(セルトリ細胞)から精子細胞へのエネルギー伝達が障害されたことによる。TCDDの作用は精嚢に焦点をあて調査中である。 3)継世代影響の分子生化学的検出: 新人為起源有害物質の継世代的影響の原因として、遺伝子不安定性をPCR法にて検出するため、反復配列DNA Pc-3をクローン化した。 4)チェルノブイリ事故による放射能汚染の遺伝的影響: 食用植物(キノコ、イチゴ等)への強度の生物学的濃縮と野性動物(カエル等)への遺伝的影響(染色体異常)が見られた。ヒトにおいても、チェルノブイリ被曝者にWT1値の高度の上昇がみられ、白血病高発の可能性を示唆した。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Nomura,T., et al.: "Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas and X-rays in Drosophila melanogaster." Jpn.J.Cancer Res.88. 461-467 (1997)
[Publications] Wada,H., et al.: "Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors." Cancer Res.57. 5379-5385 (1997)
[Publications] Li,L.Y., et al.: "Dose rate effectiveness and potentially lethal damage repair in normal and double-strand break repair deficient murine cells by γ-rays and 5 fluorouracil." Cancer Letters. 123. 227-232 (1998)
[Publications] Nakajima,H., et al.: "Radionuclides carved on the annual rings of a tree near Chernobyl." Health Physics. 74. 265-267 (1998)
[Publications] Kurooka,M., et al.: "High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice." Cancer Letters. (in press). (1998)
[Publications] Hongyo,T., et al.: "Frequent p53 Mutations at Dipyrimidine Sites in Patients with Pyothorax-associated Lymphoma." Cancer Res.(in press). (1998)
[Publications] Wang,B., et al.: "Induction of apoptosis in cultured midbrain cells from embryonic mice." Radiat.Res.147. 304-308 (1997)
[Publications] Uchida,N., et al.: "Photoreactivating enzyme for (6-4) photoproducts in the cultured goldfish cells." Photochem.Photobiol.65. 964-968 (1997)
[Publications] Namikawa,C., et al.: "Genetic linkage between the LMP2 and LMP7 genes in a teleost,medaka fish." Immunogenetics. 46. 431-433 (1997)
[Publications] Shimada,A., et al.: "Combination of genomic DNA fingerprinting into the Medaka specific-locus test system for studying environmental germ-line mutagenesis." Mutat.Res.in press (1998)
[Publications] Wada,H., et al.: "Sex-linked inheritance of the lf locus in the medaka fish (Oryzias latipes)." Zool.Sci.in press (1998)
[Publications] Fujii,T., et al.: "Increased mortality of kainic acid by pretreatment with nicardipine,a calcium channel blocker in rats." Proc.Japan Acad.73B (2). 25-29 (1997)
[Publications] Fujii,T., et al.: "Transgenerational effects of maternal exposure to chemicals on the development of the brain in the offspring." Cancer Causes and Control. 8. 524-529 (1997)
[Publications] Fujino,Y., et al.: "Low senstivity of adrenal chromaffin cells to acetylcholine,neostigmine and oxotremorine in 21-day-old rats." Jpn.J.Pharmacol.3. 157-163 (1997)
[Publications] Nakaki,T., et al.: "Nitric oxide and neurodegenerative diseases." Current Topics Pharmacol.3. 157-163 (1997)
[Publications] Inazu,N., et al.: "hCG-stimulated ovarian carbonyl reductase in relation to preovulatory ovarian follicular growth." J.Reprod.Fertil.112 (in press). (1998)
[Publications] Fukuoka,M., et al.: "Possible origin of testicular damage by phthalic acid esters." J.Toxicol.Environ.Health. 43. 21 (1997)
[Publications] Fukuoka,M., et al.: "Possible origin for testicular atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin." Jpn.J.Toxicol.Environ.Health. (in press). (1998)
[Publications] 野村大成: "未来世代を脅かすもの-ここまできた化学物質の生殖毒性" 婦人民主クラブ, 53 (1997)
[Publications] 池永満生他: "環境と健康II" へるす出版, 310 (1998)

1997 Fiscal Year Annual Research Report

新人為起源有害物質の継世代的人体影響

Principal Investigator

野村 大成 大阪大学, 医学部, 教授 (90089871)

Research Products

[Publications] Nomura,T., et al.: "Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas and X-rays in Drosophila melanogaster." Jpn.J.Cancer Res.88. 461-467 (1997)

[Publications] Wada,H., et al.: "Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors." Cancer Res.57. 5379-5385 (1997)

[Publications] Li,L.Y., et al.: "Dose rate effectiveness and potentially lethal damage repair in normal and double-strand break repair deficient murine cells by γ-rays and 5 fluorouracil." Cancer Letters. 123. 227-232 (1998)

[Publications] Nakajima,H., et al.: "Radionuclides carved on the annual rings of a tree near Chernobyl." Health Physics. 74. 265-267 (1998)

[Publications] Kurooka,M., et al.: "High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice." Cancer Letters. (in press). (1998)

[Publications] Hongyo,T., et al.: "Frequent p53 Mutations at Dipyrimidine Sites in Patients with Pyothorax-associated Lymphoma." Cancer Res.(in press). (1998)

[Publications] Wang,B., et al.: "Induction of apoptosis in cultured midbrain cells from embryonic mice." Radiat.Res.147. 304-308 (1997)

[Publications] Uchida,N., et al.: "Photoreactivating enzyme for (6-4) photoproducts in the cultured goldfish cells." Photochem.Photobiol.65. 964-968 (1997)

[Publications] Namikawa,C., et al.: "Genetic linkage between the LMP2 and LMP7 genes in a teleost,medaka fish." Immunogenetics. 46. 431-433 (1997)

[Publications] Shimada,A., et al.: "Combination of genomic DNA fingerprinting into the Medaka specific-locus test system for studying environmental germ-line mutagenesis." Mutat.Res.in press (1998)

[Publications] Wada,H., et al.: "Sex-linked inheritance of the lf locus in the medaka fish (Oryzias latipes)." Zool.Sci.in press (1998)

[Publications] Fujii,T., et al.: "Increased mortality of kainic acid by pretreatment with nicardipine,a calcium channel blocker in rats." Proc.Japan Acad.73B (2). 25-29 (1997)

[Publications] Fujii,T., et al.: "Transgenerational effects of maternal exposure to chemicals on the development of the brain in the offspring." Cancer Causes and Control. 8. 524-529 (1997)

[Publications] Fujino,Y., et al.: "Low senstivity of adrenal chromaffin cells to acetylcholine,neostigmine and oxotremorine in 21-day-old rats." Jpn.J.Pharmacol.3. 157-163 (1997)

[Publications] Nakaki,T., et al.: "Nitric oxide and neurodegenerative diseases." Current Topics Pharmacol.3. 157-163 (1997)

[Publications] Inazu,N., et al.: "hCG-stimulated ovarian carbonyl reductase in relation to preovulatory ovarian follicular growth." J.Reprod.Fertil.112 (in press). (1998)

[Publications] Fukuoka,M., et al.: "Possible origin of testicular damage by phthalic acid esters." J.Toxicol.Environ.Health. 43. 21 (1997)

[Publications] Fukuoka,M., et al.: "Possible origin for testicular atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin." Jpn.J.Toxicol.Environ.Health. (in press). (1998)

[Publications] 野村大成: "未来世代を脅かすもの-ここまできた化学物質の生殖毒性" 婦人民主クラブ, 53 (1997)

[Publications] 池永満生 他: "環境と健康II" へるす出版, 310 (1998)

野村大成大阪大学, 医学部, 教授 (90089871)

[Publications] 池永満生他: "環境と健康II" へるす出版, 310 (1998)