巻号一覧
5 巻, Supplement 号
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森雪 弘文, 市村 正道1980 年 5 巻 Supplement 号 p. 1-9
発行日: 1980/12/25
公開日: 2008/02/21
ジャーナル フリーA new anti-tumor polysaccharide, lentinan (β-1, 3 Glucan) was studied on the acute toxicities using both sexes of mice (ICR) and rats (CD) treated by intravenously (i.v.), intraperitoneally (i.p.), subcutaneously (s.c.) and orally (p.o.). LD50 values in mg/kg body weight were essentially the same regardless of species as well as sexes and estimated a; follows : 250-500 (i.v.), >2500 (i.p., s.c., and p.o.). Cyanosis, convulsion and death were observed in both species of animals administered (i.v.) with only higher dosages of lentinan. No remarkable toxic signs being specific from lentinan were observed in any cases of treatment, i.p., s.c. and p.o. Gross findings : enlargement of the spleen (i.v.; i.p., s.c.) and coarse nodular surface of the kidneys (i.v.) in the both species of animals, erythema of the ears (i.v., i.p., s.c.) in mice, petechial hemorrhage of the lung and abdomen (i.v.), enlargement of the mesentric lymphonodes (i.v.) and edema of the diaphragm and intestine (i.p.) in rats were observed. In parallel, another sample of lentinan for clinical use prepared by freeze-dried procedure was tested in both sexes of mice and rats treated by i.v. alone, comparing with a original sample mentioned above. So far as the acute toxicities of lentinans concerned, no significant differences between two preparations were observed.抄録全体を表示PDF形式でダウンロード (633K) -
石井 胖行, 宇佐美 洲治, 藤本 積, 森雪 弘文, 橋本 重文, 市村 正道1980 年 5 巻 Supplement 号 p. 11-31
発行日: 1980/12/25
公開日: 2008/02/21
ジャーナル フリーMale and female JCL:SD rats were treated intravenously with lentinan in 5% mannitol solusion at dose levels of 0, 0.03, 3.0 and 30.0 mg/kg/day for 5 weeks. Rats receiving 0.3, 3.0 and 30.0 mg/kg/day showed reddening in ear, tail and scrotum and edema in legs and scrotum after day 3 of treatment. Males receiving 30.0 mg/kg/day gained less body weight than control. Occult blood was found in the urine of rats receiving 30.0 mg/kg/day. With regard to haematology, rats from the treatment groups had low mean values relating to red blood cell count, packed cell volume and haemoglobin, while high white blood cell count were recorded for these rats. Biochemical examinations revealed decreases in albumin level and A/G ratio and increases in β-globulin and γ-globulin levels for rats from the treatment groups. Slightly high values of BUN were showed for rats receiving 30.0 mg/kg/day. Organ weight analysis showed dose-dependent increase in the spleen, liver and adrenal. Histopathological changes attributable to treatment included (1) changes in reticuloendothelial system such as proliferation of reticular cells and micronodule of epithelioid cells in the spleen, liver and lymph nodes; (2) arteritis in many organs especially notable in epididymis, intestines and mesentery ;(3) haemorrhagic changes in lung, intestines and urinary bladder and secondary changes such as increased chronic nephropathy, hypospermatogenesis, spermatic granuloma in epididymis and granulomatous inflammation in ear, tail and scrotum. The maximum safe dose was estimated to be smaller than 0.03 mg/kg/day for males and 0.03 mg/kg/day for females in the present study.抄録全体を表示PDF形式でダウンロード (1982K) -
島津 肇, 武田 京一, 小野寺 千秋, 牧田 市郎, 橋 高志, 山添 武司, 国場 幸史, 谷川 広行, 大熊 新一, 新保 幸太郎, ...1980 年 5 巻 Supplement 号 p. 33-57
発行日: 1980/12/25
公開日: 2008/02/21
ジャーナル フリーChronic toxicity of lentinan was studied in male and female JCL:SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophile count and platelet count, and an increase in serum β-globilin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endthelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung ; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.抄録全体を表示PDF形式でダウンロード (3459K) -
小原 佑一1980 年 5 巻 Supplement 号 p. 59-72
発行日: 1980/12/25
公開日: 2008/02/21
ジャーナル フリーWilzbach法による3H交換反応で得られた〔3H(G)-lentinanをマウス, ラット, イヌに静脈内投与してlentinanの生体内運命を調べた。1) 血中濃度は投与直後すみやかに減少し, その後ゆっくりと減少するという二相性を示した。2) 呼気への排泄はほとんどなく, 投与初期に一時的に尿中への排泄が高いほかは尿, 糞中に長期間にわたって少しづつ排泄された。3)臓器分布は肝臓, 脾臓等RES系細胞の富む組織に多くとり込まれ, 投与初期に比較的多かった腎臓, 肺はその後減少した。投与1年以上経過すると肝臓, 脾臓への残留もわずかであった。4) Sarcoma-180腫瘍組織への特異的とり込みは見られなかった。5) マウス, ラット, イヌの間に種差は見出せなかった。6) 現在まで報告されている代謝されにくい高分子多糖体や溶連菌製剤のような他の悪性腫瘍免疫療剤の生体内運命と本質的には同じと思われる。抄録全体を表示PDF形式でダウンロード (816K) -
小原 佑一1980 年 5 巻 Supplement 号 p. 73-80
発行日: 1980/12/25
公開日: 2008/02/21
ジャーナル フリー[methyl-3H]-dimethyl sulfateでlentinanを3H-methyl化して得られたmethyl化率0.011%の [methyl-3H]-methyl lentinanをlentinanに添加して生体内運命を調べた。1) 血中濃度は投与直後すみやかに減少し, その後ゆっくりと減少するという二相性を示した。2) 呼気中への排泄は少く, 尿中排泄は投与初期に一時的に排泄が多く, その後長期にわたって少しづつ排泄された。3) 臓器分布は肝臓, 脾臓, 腸間膜リンパ節RES系細胞の富む組織に多くとり込まれた。初期に比較的多かった腎臓, 肺もその後減少した。肝臓, 脾臓, 腸間膜リンパ節についても時間の経過と共に減少した。4) 連続投与をおこなった場合, 臓器への分布は単回投与と同じ傾向であるが肝臓, 脾臓等について量的には少い傾向であった。5) 胆汁排泄は48時間で約2.6%とわずかであった。5) 胎仔移行は胎仔, 新生仔1匹当り母獣に投与したものの0.2%以下とわずかであった。6) 乳汁移行は乳汁1 ml当り0.08%とほとんどみられなかった。Lentinanの生体内運命は現在まで報告されている代謝されにくい高分子多糖や溶連菌製剤のような他の悪性腫瘍免疫療法剤の生体内運命と類似している。抄録全体を表示PDF形式でダウンロード (573K)
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