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1.
Chemoprevention by amiloride of experimental carcinogenesis in rat colon induced by azoxymethane 总被引:1,自引:0,他引:1
Tatsuta Masaharu; Iishi Hiroyasu; Baba Miyako; Uehara Hiroyuki; Nakaizumi Akihiko 《Carcinogenesis》1995,16(4):941-942
The effects of amiloride on the incidence and histology of colontumors induced by azoxymethane, on the labeling index of thecolon mucosa and on the activity of ornithine decarboxylasein the colon wall were investigated in Wistar rats. Rats received10 weekly injections of 7.4 mg/kg body wt azoxymethane and s.c.injections of 5 or 7.5 mg/kg body wt amiloride in depot formevery other day for 35 weeks. Prolonged administration of amilorideat a dose of 7.5 mg/kg, but not 5 mg/kg, significantly reducedthe incidence of colon tumors at week 35. However, administrationof amiloride had little or no significant influence on the histologicaltypes of colon tumors and cancers. Administration of amilorideat 7.5 mg/kg significantly decreased the labeling index of thecolon mucosa and ornithine decarboxylase activity in the colonwall during and after administration of azoxymethane. Thesefindings suggest that amiloride inhibits development of colontumors. A possible mechanism of inhibition of colon carcinogenesisby amiloride is its suppression of proliferation of colon tumorcells. 相似文献
2.
Narahara H Tatsuta M Iishi H Baba M Uedo N Sakai N Yano H Ishiguro S 《International journal of cancer. Journal international du cancer》2000,88(2):157-161
The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation. 相似文献
3.
Enhancement by the tricyclic antidepressant, desipramine, of experimental carcinogenesis in rat colon induced by azoxymethane 总被引:2,自引:0,他引:2
The effects of the tricyclic antidepressant drug desipramineon the incidence, number and histology of colon tumors inducedby azoxymethane (AOM), and on the serum norepinephrine (NE)concentration and the labeling index of colon mucosa were investigatedin Wistar rats. Rats were treated s.c. with 7.4 mg AOM/kg bodywt once a week for 10 weeks, and also s.c. with 10 mg desipraminehydrochloride (desipramine)/kg body weight until the end ofthe experiment. Treatment with desipramine significantly increasedthe incidence, but not the number, of colon tumors in week 35.However, it did not influence the location and the histologicalappearance of the colon tumors or the histological types ofcolon adenocarcinomas. Furthermore, it significantly increasedthe serum NE level and the labeling index of colon mucosa duringand after AOM treatment. These findings indicate that desipramineenhanced the development of colon tumors and that its effectmay be related to its effect in increasing proliferation ofcolon epithelial cells. 相似文献
4.
The effect of the opioid receptor agonist methionine enkephalin (Met-enkephalin) and the opioid receptor antagonist naloxone on colonic carcinogenesis induced by azoxymethane was investigated in Wistar rats. Rats received ten weekly injections of 7.4 mg/kg of body weight of azoxymethane and injections of Met-enkephalin (50 micrograms/kg of body weight), naloxone (2 mg/kg of body weight), or Met-enkephalin (50 micrograms/kg of body weight) plus naloxone (2 mg/kg of body weight) once every 2 days. In wk 40, the group treated with Met-enkephalin had a significantly increased incidence of colonic tumors. A combination of Met-enkephalin and naloxone attenuated the enhancing effect by Met-enkephalin on the development of colonic tumors. Administration of naloxone alone had no influence on colonic tumorigenesis. During and after administration of the carcinogen, the bromodeoxyuridine-labeling indices of the colon mucosa and/or cancers were significantly increased in rats treated with Met-enkephalin. However, a combination of Met-enkephalin and naloxone significantly decreased the labeling indices of the colon mucosa and/or cancers. These findings indicate that Met-enkephalin enhanced colon carcinogenesis and that naloxone attenuated this enhancement. Because naloxone is an opioid receptor antagonist, these findings also indicate that the enhancing effect of Met-enkephalin on colon carcinogenesis may be mediated through opioid receptors. 相似文献
5.
M Tatsuta H Iishi M Baba M Ichii A Nakaizumi H Uehara H Taniguchi 《International journal of cancer. Journal international du cancer》1991,47(5):738-741
The effects of putrescine on the incidence and number of colon tumors induced by azoxymethane, and on the labelling index and the activity of ornithine decarboxylase (ODC) in the colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 300 mumol/kg body weight of putrescine every 2 days until the end of the experiment at week 40. This prolonged treatment with putrescine significantly reduced the incidence and number of colon tumors. Administration of putrescine also significantly decreased the labelling index and the ODC activity in the colon mucosa during, but not after, treatment with the carcinogen. These last effects may be related to the action of putrescine in inhibiting the development of colonic tumors. 相似文献
6.
M Tatsuta H Iishi M Baba H Taniguchi 《International journal of cancer. Journal international du cancer》1992,50(1):108-111
The effects of ad libitum feeding of synthetic, low-protein diets on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), on the norepinephrine concentration in the colon wall tissue and on the labelling index of colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and were given synthetic diets of equal calorie content containing 25% casein (normal-protein diet), 10% casein (low-protein diet) or 5% casein (very-low-protein diet). Administration of the low- and very-low-protein diets resulted in significant increases in the incidence and number of colon tumors at week 30. However, it did not affect the histology of the colon tumors. The low- and very-low-protein diets also resulted in significant increases in norepinephrine concentration in the proximal and distal portions of the colon wall and in the labelling indices of both parts of the colon mucosa. Our findings indicate that low- and very-low-protein diets enhance colon carcinogenesis and that this may be related to their effects in increasing the norepinephrine level in the colon wall and in stimulating proliferation of colon epithelial cells. 相似文献
7.
The effects of vasoactive intestinal peptide (VIP) on the incidence and histology of colonic tumors induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 20 micrograms/kg body weight of VIP every other day for 12 weeks and from experimental week 3, were given 10 weekly injections of 7.4 mg/kg body weight of AOM. The administration of VIP before and during AOM treatment resulted in a significant increase in the incidence of colonic tumors in week 40. Furthermore, it caused a significant increase in the labeling index of the colonic mucosa during AOM treatment. These findings indicate that VIP enhanced the development of colonic tumors. This effect may have been related to its effect in increasing proliferation of cells in the colonic mucosa during administration of the carcinogen. 相似文献
8.
M Tatsuta H Iishi M Baba H Taniguchi 《International journal of cancer. Journal international du cancer》1989,44(6):1008-1011
The effects of cysteamine (2-aminoethanethiol hydrochloride) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the norepinephrine concentration in the colon wall tissue and the labelling indices of colon mucosa and colon cancers were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and alternate-day subcutaneous injections of 25 mg/kg of cysteamine in 0.9% NaCl solution until the end of the experiment. At week 40, prolonged administration of cysteamine significantly reduced the incidence and number of colon tumors. Histologically, the adenocarcinomas that did develop in rats treated with cysteamine exhibited high mucin-producing activity. Administration of cysteamine caused significant decreases in the norepinephrine concentration in colon tissue and in the labelling indices of colon mucosa and cancers. Our findings indicate that cysteamine inhibits the development of colon tumors. This action may be related to its effect in decreasing norepinephrine concentration in the colon wall tissues and subsequently in decreasing proliferation of colon cancer cells. 相似文献
9.
Enhancement by bombesin of colon carcinogenesis and metastasis induced by azoxymethane in Wistar rats. 总被引:2,自引:0,他引:2
H Iishi M Tatsuta M Baba R Yamamoto H Taniguchi 《International journal of cancer. Journal international du cancer》1992,50(5):834-839
The effects of bombesin on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on their metastases to the peritoneum and/or lymph nodes, were investigated in Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, and s.c. injections of bombesin in depot form every other day until the end of the experiment in week 30. Administration of bombesin significantly increased the incidence of colon tumors in week 30. It had no influence on the histological features or depths of involvement of colon adenocarcinomas, but significantly increased the incidence of cancer metastasis to the peritoneum and/or lymph nodes. It also caused a significant increase in the labeling index of the colon epithelial cells. Our findings indicate that bombesin enhances the development and metastasis of colon tumors, and that this effect may be related to its effect in increasing proliferation of epithelial cells of the colon. 相似文献
10.
M Tatsuta H Iishi M Baba M Ichii A Nakaizumi H Uehara H Taniguchi 《Cancer research》1990,50(17):5308-5311
The effect of bromocriptine on inhibition by cysteamine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. After 25 weeks of p.o. treatment with N-methyl-N'-nitro-N-nitrosoguanidine, rats were given injections every other day: cysteamine (50 mg/kg body weight); cysteamine (50 mg/kg body weight) plus bromocriptine (0.5 or 0.25 mg/kg body weight); or bromocriptine (0.5 or 0.25 mg/kg body weight). In week 52, the group treated with cysteamine showed a significantly decreased incidence of gastric cancers. Concomitant treatment with bromocriptine at 0.5 but not at 0.25 mg/kg body weight significantly attenuated the inhibitory effect of cysteamine on gastric carcinogenesis. Administration of bromocriptine alone at either dosage had no influence on gastric carcinogenesis. The labeling index of the antral mucosa was significantly reduced in rats treated with cysteamine and significantly higher in those treated concomitantly with bromocriptine at 0.5 mg/kg body weight than in those treated with cysteamine alone. These findings indicate that cysteamine suppressed gastric carcinogenesis and that bromocriptine at high dosage attenuated this inhibition. These findings also suggest that dopamine is involved in the mechanism of inhibition of gastric carcinogenesis by cysteamine. 相似文献
11.
Hiroyasu Iishi Masaharu Tatsuta Miyako Baba Hiroyuki Uehara Akihiko Nakaizumi Hitoshi Akedo 《Cancer science》1996,87(7):730-734
The effects of combined administration of bombesin and the diuretic triamterene on the incidence of peritoneal metastasis of intestinal cancers induced by azoxymethane (AOM) and the labeling index of intestinal cancers were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of AOM (7.4 mg/kg body weight) for 10 weeks and s.c. injections of bombesin (40 μg/kg body weight) every other day, and from week 16, s.c. injections of triamterene (10 and 20 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of both doses of triamterene with bombesin had little or no influence on the enhancement of intestinal carcinogenesis by bombesin, or the location, histologic type, depth of invasion, or labeling index of intestinal cancers, it significantly reduced the incidence of cancer metastasis. These findings indicate that triamterene suppresses cancer metastasis through a mechanism that does not affect the proliferation of intestinal cancers. 相似文献
12.
Enhancement by thyroxine of experimental carcinogenesis induced in rat colon by azoxymethane. 总被引:2,自引:0,他引:2
H Iishi M Tatsuta M Baba S Okuda H Taniguchi 《International journal of cancer. Journal international du cancer》1992,50(6):974-976
The effect of thyroxine (T4) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats were given AOM by injection once a week for 10 weeks, together with T4 in depot form until the end of the experiment. Administration of T4 resulted in a significant increase in the incidence of colon tumors in week 35. However, it did not influence the histological appearance of the colon tumors or the histological types and depths of involvement of colon adenocarcinomas. Furthermore, it caused a significant increase in the labeling index of the colon during, but not after, AOM treatment. Our findings indicate that T4 enhances the development of colon tumors, which may be related to its effect in increasing proliferation of epithelial cells in the colon mucosa during administration of the carcinogen. 相似文献
13.
K Iseki M Tatsuta H Uehara H Iishi H Yano N Sakai S Ishiguro 《International journal of cancer. Journal international du cancer》1999,81(5):730-733
The effects of 1alpha-hydroxyvitamin D3[1alpha(OH)D3] and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] on the incidence of colon tumors induced by azoxymethane and on the labeling index and angiogenesis of colon tumors were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 1alpha(OH)D3 and 1,25(OH)2D3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1alpha(OH)D3 and 1,25(OH)2D3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1alpha(OH)D3 or 1,25(OH)2D3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1alpha(OH)D3 and 1,25(OH)2D3 at higher doses significantly decreased the labeling index, the immuno-histochemical staining for vascular endothelial growth factor and microvessel counts in colon tumors. Our findings suggest that both 1alpha(OH)D3 and 1,25(OH)2D3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1alpha(OH)D3 and 1,25(OH)2D3 is the inhibition of angiogenesis as well as an anti-proliferative effect. 相似文献
14.
Hiroyasu Iishi Masaharu Tatsuta Miyako Baba Hiroyuki Uehara Akihiko Nakaizumi 《International journal of cancer. Journal international du cancer》1994,58(4):533-537
The effects of combined administration of bombesin (40 μ/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum. 相似文献
15.
The effects of the dopamine agonist 2-bromo-alpha-ergocryptine methanesulfonate (bromocriptine) on the incidence, number and histology of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in Wistar rats. Rats were given 1 or 2 mg kg-1 body weight of bromocriptine subcutaneously every other day in depot form after 25 weeks of oral treatment with MNNG. Prolonged administration of bromocriptine at both dosages every other day resulted in a significant increase in the incidence and number of gastric cancers of the glandular stomach by week 52. Bromocriptine treatment did not influence the histological type of gastric cancer, but caused a significant increase in the labelling index of epithelial cells of the antrum. These findings indicate that the dopamine agonist bromocriptine promotes gastric carcinogenesis, and that this effect may be related to its effect in increasing proliferation of epithelial cells in the antral mucosa. 相似文献
16.
M Tatsuta H Iishi M Baba H Taniguchi 《International journal of cancer. Journal international du cancer》1992,50(2):298-301
The effects of 6-hydroxydopamine (6-OHDA) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on norepinephrine (NE) concentration in the colon wall and the labelling index of the colon mucosa were investigated in Wistar rats. Rats received sub-cutaneous (s.c.) injections of AOM once a week for 10 weeks, and throughout 35 weeks were also given intraperitoneal (i.p.) injections of 6-OHDA. Prolonged administration of 6-OHDA was found to cause a significant reduction in the incidence and number of colon tumors. However, it had no influence on the histological features or depths of involvement of colon tumors and/or adenocarcinomas. Its administration also caused significant decreases in the NE concentration in the colon wall and in the labelling index of the colon mucosa. Our findings indicate that 6-OHDA has a protective effect against colon carcinogenesis, and that the activity of the sympathetic nervous system may have an important influence on colon carcinogenesis. 相似文献
17.
Enhancement by neurotensin of experimental carcinogenesis induced in rat colon by azoxymethane 总被引:2,自引:0,他引:2
The effects of neurotensin on the incidence, number, size, and histology of colon tumours induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 10 weekly injections of AOM (7.4 mg kg-1 body weight) and were also given 200 micrograms kg-1 of neurotensin in depot form every other day until the end of the experiment. In week 40, prolonged alternate-day administration of neurotensin resulted in significant increases in the number and size of colon tumours and the incidence of adenocarcinomas penetrating muscle layer and deeper. However, neurotensin did not influence the incidence of tumour-bearing rats and the histological appearance of colon tumours. Administration of neurotensin caused a significant increase in the labelling index of the colon cancers but not that of colon mucosa. These findings indicate that neurotensin enhanced the growth of colon tumours, possibly related to its effect in increasing proliferation of colon cancer cells. 相似文献
18.
The effects of the calmodulin antagonist trifluoperazine on the development of colon tumors induced by azoxymethane (AOM), and on the labeling index of the colon mucosa and the activity of ornithine decarboxylase (ODC) in the colon wall were investigated in Wistar rats. Prolonged administration of trifluoperazine significantly reduced the number of colon tumors in week 35. Administration of trifluoperazine caused a significant decrease in the labeling index of the colon mucosa and the AOM-induced ODC activity in the colon wall during administration of the carcinogen, but not after its cessation. A possible mechanism of inhibition of colon carcinogenesis by trifluoperazine could be its inhibition of AOM-induced increase in ODC activity of the colon wall with consequent suppression of cell proliferation in the colon. 相似文献
19.
Hiroyasu Iishi Masaharu Tatsuta Miyako Baba Hiroyuki Uehara Hiroyuki Yano Akihiko Nakaizumi 《International journal of cancer. Journal international du cancer》1995,61(6):861-863
The effects of the neuropeptide galanin on the development of colon tumors induced by azoxymethane (AOM) and on the labeling index of colon epithelial cells were investigated in Wistar rats. Treatment with galanin significantly decreased the incidence of colon tumors at week 45. Galanin did not influence the histological appearance of the colon tumors, but it slightly increased the frequency of sub-mucosal adenocarcinomas. Furthermore, it significantly decreased the labeling index of colon mucosa during and after AOM treatment. These findings indicate that galanin inhibited the development of colon tumors and that this effect may be related to its suppression of colon-epithelial-cell proliferation. © 1995 Wiley-Liss, Inc. 相似文献
20.
Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats 总被引:3,自引:0,他引:3
Iishi H Tatsuta M Baba M Yano H Sakai N Akedo H 《International journal of cancer. Journal international du cancer》2000,86(3):416-420
The effects of the soybean isoflavonoid genistein on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane (AOM) were investigated in male inbred Wistar rats. From the beginning of the experiment, rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c. injections of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of genistein (5 or 10 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and of cancer metastasis to the peritoneum. Although genistein administered at either dose had little or no effect on the enhancement of intestinal carcinogenesis by bombesin or on the location, histologic type, depth of involvement, labeling index, or growth pattern of intestinal cancers, it significantly decreased the incidence of cancer metastasis. Genistein also significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. Our findings indicate that genistein attenuates cancer metastasis by inhibiting cancer cell invasion into lymphatic vessels through activities that do not affect the growth of intestinal cancers. 相似文献