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PubMed1987

Effects of timing and quantity of chronic dietary ethanol consumption on azoxymethane-induced colonic carcinogenesis and azoxymethane metabolism in Fischer 344 rats.

Epidemiological studies have shown an association between consumption of alcoholic beverages and carcinoma of the large bowel, but studies in experimental models of colonic carcinogenesis have yielded conflicting results. We assessed the effects on azoxymethane-induced colonic carcinogenesis of both timing of chronic dietary ethanol consumption relative to carcinogen administration and quantity of ethanol consumption. Ten-week-old male Fischer 344 rats were given 11%, 22%, or 33% of calories as reagent ethanol or no ethanol by pair feeding with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. Ten weekly s.c. injections of the bowel carcinogen azoxymethane (AOM), 7 mg/kg, were given to all rats in weeks 1-10. Three experimental groups were given their respective ethanol diet during acclimatization and AOM administration (preinduction and induction phases) and then were given the no-ethanol diet from week 11 until sacrifice in week 26 (postinduction phase). Three other groups received the no-ethanol diet during acclimatization and AOM administration and then were changed to their respective ethanol diet until sacrifice. The control AOM group received the no-ethanol diet throughout the study. Suppression of colonic tumorigenesis occurred in the groups with high levels of chronic dietary ethanol consumption during acclimatization and AOM administration: in the 33% and 22% diet groups, the prevalence of colonic tumors was 3% and 20% as compared with 50% in control (P less than 0.001 and P less than 0.02, respectively). Tumorigenesis in the left colon was more affected than in the right colon, as tumor prevalence in the left colon was decreased in both the 33% and 22% diet groups (0% in both versus 24% in control, P less than 0.005), whereas prevalence in the right colon was decreased only in the 33% diet group (3% versus 38%, P less than 0.001). By contrast, prevalence of colonic tumors in the 11% diet group was not significantly different from control. Chronic dietary ethanol consumption after AOM administration had no effect on tumor outcome, regardless of quantity of consumption. In an analogous study of [14C]AOM metabolism in rats fed the 33% diet during acclimatization and AOM administration, 14CO2 was exhaled at a slower rate than in rats fed no-ethanol diet (P = 0.05), indicating suppression of AOM metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Prevention by chemopreventive agents of azoxymethane-induced foci of aberrant crypts in rat colon.

Foci of aberrant crypts are putative preneoplastic lesions of colon cancer that can be detected in unsectioned colons stained with methylene blue. The ability of this assay to demonstrate chemopreventive activity was evaluated. Male Sprague-Dawley rats received two subcutaneous injections 1 week apart, of 15 mg/kg azoxymethane each. The animals started to receive the test agents in their diet 1 week prior to the first injection of azoxymethane and continuously until killed 5 weeks later. The number of foci of aberrant crypts induced by the treatment of azoxymethane was reduced from 228 foci/animal without any chemopreventive agent to 151 foci/animal by N-acetylcysteine; to 121 foci/animal by dehydroepiandrosterone; to 161 by alpha-difluoromethylornithine; and to 121 by 1,2-oxothiazolidine-4-carboxylate. The other agents (diallyl sulfide, ellagic acid and phenethyl isothiocyanate) did not significantly alter the number of foci/animal induced by azoxymethane. Animals that did not receive azoxymethane had an average of 0.72 foci/animal. Our results suggest that four of the tested agents might reduce azoxymethane-induced colon cancer, which requires confirmation. Further validation of the foci of aberrant crypt in the colon assay to screen chemicals for chemoprevention agents is warranted.

Acetylcysteine↗
PubMed2000

Age-dependent induction of aberrant crypt foci in rat colon by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and azoxymethane.

Pups and adult rats received seven oral exposures (three time weekly) of the food mutagen PhIP (50 mg/kg), or two subcutaneous exposures (once weekly) of the experimental carcinogen azoxymethane (3.75 mg/kg). Aberrant crypt foci (ACF) were scored 8 weeks after the first exposure. In addition, lactating dams with suckling pups were orally exposed to 50 mg/kg of PhIP, three times weekly for three weeks. Direct PhIP exposure of pups induced 2.2 times more ACF than similar exposure of adult rats (2.0+/-0.0 versus 0.9+/-0.8, P<0.05). The growth of ACF, expressed as crypt multiplicity AC/ACF, was 3.5 times larger in neonatally exposed rats than in rats exposed in adulthood (8.0+/-7.3 versus 2.3+/-1.6, P<0.05). PhIP exposure via breast milk induced ACF in 3 of 25 animals. However, the difference versus controls, which had no ACF, did not reach statistical significance. Contrary to PhIP, azoxymethane induced more ACF in adult rats than in pups (2.8+/-1.9 versus 4.8+/-1.7, P<0.05). Similarly to PhIP however, azoxymethane induced 3.2 times larger ACF (AC/ACF) in pups than in adult rats (11.9+/-8.4 versus 3.7+/-1.9, P<0.001). Whereas no PhIP-induced ACF (0/15) were observed in the lymphoid follicles, approximately 60% of the azoxymethane-induced ACF (32/56) were located in these structures. This difference was statistically significant (P<0.001). The density of azoxymethane-induced ACF was 80 times larger in the lymphoid follicles than in the surrounding mucosa (P<0.01). Based on the assumption that the formation of ACF with high multiplicity is predicative for the tumour development we conclude that neonatal rats are more susceptible to PhIP and azoxymethane than adult rats.

Aging↗
PubMed2007

Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats.

PURPOSE: Epidemiologic studies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory animal model studies have provided evidence that stilbenes, phenolic compounds present in grapes and blueberries, play a role in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for its preventive activity against colon carcinogenesis. EXPERIMENTAL DESIGN: Experiments were designed to study the inhibitory effect of pterostilbene against the formation of azoxymethane-induced colonic aberrant crypt foci (ACF) preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental diets containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed, and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen. Effects on mucin MUC2 were also determined. RESULTS: Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane-induced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane-induced colonic cell proliferation and iNOS expression. Inhibition of iNOS expression by pterostilbene was confirmed in cultured human colon cancer cells. CONCLUSIONS: The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for the prevention of colon cancer.

Animals↗
PubMed1984

The effect of deuterium substitution on carcinogenesis by azoxymethane.

Azoxymethane was synthesized labeled with deuterium in one or other of the two methyl groups. Groups of 20 male F344 rats were given either 4 mg or 1 mg per week of each of the labeled compounds or of unlabeled azoxymethane each week in drinking water, for 30 weeks, after which the animals were kept until they died. All in the high dose groups died earlier with tumors induced by the treatment than did those in the low dose groups. Azoxymethane itself led to earlier death than either of the deuterium-labeled compounds, and methylazoxymethane-d3 seemed to be the least potent compound. The incidence of liver tumors and of kidney tumors was similar in the groups receiving the same dose of all 3 compounds. However, there were fewer tumors of the colon in animals given methyl-d3-azoxymethane than with the other 2 compounds. These results are consistent with the concept that either methyl group of azoxymethane can be oxidized in the course of activation to a proximate carcinogenic agent for liver, kidney or colon of rats, but that oxidation of the methyl group next to the nitrogen bearing oxygen is more important in the induction of colon tumors.

Animals↗
PubMed1985

Goblet cell changes during intestinal adaptation to azoxymethane and enteric bypass in the rat.

Numbers of intestinal goblet cells containing specific acid mucins were determined in male Sprague-Dawley rats receiving azoxymethane (total dose 90 mg kg-1) with or without jejunoileal bypass (JIB). Controls had injections of vehicle and sham bypass. Thirty weeks postoperatively colorectal length and crypt depth were increased by azoxymethane and further increased by JIB. JIB doubled the yield of intestinal tumours (P less than 0.01). Goblet cells containing sulphomucins normally predominated throughout the intestinal tract. Contents of sulphomucins and especially sialomucins were consistently higher in the small bowel and colon of rats receiving azoxymethane alone, but again the highest values were observed in animals with azoxymethane plus JIB. Both small-bowel bypass and azoxymethane stimulate adaptive growth of the colon and small bowel remaining in circuit. Goblet-cell hyperplasia is a feature of this response, and sialomucins are preferentially secreted by the adapting epithelium.

Animals↗
PubMed2005

Tissue-specific attenuation of endogenous DNA I-compounds in rats by carcinogen azoxymethane: possible role of dietary fish oil in colon cancer prevention.

I-compounds are bulky covalent DNA modifications that are derived from metabolic intermediates of nutrients. Some I-compounds may play protective roles against cancer, aging, and degenerative diseases. Many carcinogens and tumor promoters significantly reduce I-compound levels gradually during carcinogenesis. Colon cancer is the second leading cause of cancer death in the United States, whereas cancer of the small intestine is relatively rare. Here we have studied levels of I-compounds in DNA of colon and duodenum of male Sprague-Dawley rats treated with azoxymethane. The effects of dietary lipids (fish oil or corn oil) on colon and duodenal DNA I-compounds were also investigated. Rats fed a diet containing fish oil or corn oil were treated with 15 mg/kg azoxymethane. Animals were terminated 0, 6, 9, 12, or 24 hours after injection. I-compound levels were analyzed by the nuclease P1-enhanced (32)P-postlabeling assay. Rats treated with azoxymethane displayed lower levels of I-compounds in colon DNA compared with control groups (0 hour). However, I-compound levels in duodenal DNA were not diminished after azoxymethane treatment. Animals fed a fish oil diet showed higher levels of I-compounds in colonic DNA compared with corn oil groups (mean adduct levels for fish and corn oil groups were 13.35 and 10.69 in 10(9) nucleotides, respectively, P = 0.034). Taken together, these results support claims that fish oil, which contains a high level of omega-3 polyunsaturated fatty acids, may have potent chemopreventive effects on carcinogen-induced colon cancer. The fact that duodenal I-compounds were not diminished by azoxymethane treatment may have been due to the existence of tissue-specific factors protecting against carcinogenesis. In conclusion, our observations show that endogenous DNA adducts may serve not only as sensitive biomarkers in carcinogenesis and cancer prevention studies, but are also helpful to further our understanding of the chemopreventive properties of omega-3 fatty acids and mechanisms of carcinogenesis.

Analysis of Variance↗
PubMed2002

Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure.

Fulminant hepatic failure (FHF) in humans produces a bleeding diathesis due in large part to a reduction in the biosynthesis of liver-derived coagulation factors. Remarkably, factor VIII procoagulant activity is elevated in most of these patients despite widespread liver cell death. FHF can be modeled in mice by administration of azoxymethane, the active ingredient found in cycad palm nuts. We compared the expression of factor VIII to other hepatic hemostatic factors in azoxymethane-induced murine FHF. Mice displayed dose-dependent decreases in all coagulation factor activities measured, including factors V, VII, VIII, and IX. At the highest dose of azoxymethane (50 microg/g body weight), factor VIII activity in plasma decreased by 98% within 36 hours after treatment, which was associated with an 80% reduction in hepatic factor VIII messenger RNA (mRNA). In contrast, factor VIII mRNA levels in spleen, kidney, and lung tissue of azoxymethane-treated mice were unchanged. Cellular damage in these mice appeared to be limited to hepatocytes as evident by histologic examination. This finding is supported by 2 observations. First, hepatic mRNA levels of von Willebrand factor, which is synthesized by liver sinusoidal endothelial cells but not hepatocytes, were unchanged. Second, von Willebrand factor was detected antigenically in liver sections of azoxymethane-treated mice by immunofluorescence. These results indicate that the contribution of the liver to factor VIII biosynthesis is not replaced or significantly supplemented by other tissues in this model of FHF.

Animals↗
PubMed1975

Effect of dietary beef fat on intestinal tumor formation by azoxymethane in rats.

Two groups of 20 male Sprague-Dawley rats each were given azoxymethane subcutaneously (8 mg/kg body wt) and fed a normal diet or one high in beef fat. Control groups were not given azoxymethane. The rats on the fat diet consumed less food and gained significantly more weight than the animals on the normal diet. Those given high fat and azoxymethane developed more intestinal tumors than did the dietary controls receiving the carcinogen. Furthermore, they had a greater number of larger tumors and more metastases than did the animals fed normally. No intestinal tumors were observed in control groups not receiving azoxymethane. The results show that the diet high in beef fat enhances the carcinogenic effect of azoxymethane in the rat.

Animals↗
PubMed1996

Suppression of azoxymethane-induced aberrant crypt foci in rat colon by nimesulide, a selective inhibitor of cyclooxygenase 2.

Non-steroidal anti-inflammatory drugs, such as piroxicam and sulindac, are known to inhibit development of aberrant crypt foci (ACF) and cancer in the colon. However, these agents cause gastrointestinal side-effects. Nimesulide is a selective inhibitor of cyclooxygenase 2 and has been shown to have a more potent anti-inflammatory action than piroxicam, but be less ulcerogenic and, therefore, a potentially more useful chemopreventive agent. To assess this possibility the inhibitory effects of nimesulide on the formation of ACF induced by azoxymethane in rat colon were investigated, and compared with those of piroxicam and sulindac. Male F344 rats were treated s.c. with 15 mg/kg body weight azoxymethane once a week for 2 weeks and given 50, 100 or 200 ppm nimesulide, 200 ppm piroxicam, or 200 ppm sulindac in their diet from the day before the first carcinogen treatment until the end of the experiment at week 4. At this time, nimesulide at doses of 50, 100 and 200 ppm had reduced the numbers of azoxymethane-induced ACF to 75%, 71% and 65% respectively compared to the control. The number of azoxymethane-induced ACF per colon in the group given 200 ppm nimesulide was almost the same as in those given 200 piroxicam, and lower than that in the group given 200 ppm sulindac. These results suggest that nimesulide, a selective cyclooxygenase 2 inhibitor, warrants attention as a candidate for chemopreventive agent with low toxicity, active against colon carcinogenesis.

Animals↗
PubMed1989

Early alterations of rat intestinal diamine oxidase activity by azoxymethane, an intestinal carcinogen.

Some mutagenic hydrazino compounds are also diamine oxidase inhibitors. Therefore, this interrelationship was studied for the intestinal carcinogen azoxymethane. In vitro, azoxymethane was a very weak inhibitor of rat intestinal diamine oxidase activity. In vivo, after subcutaneous injection of a single dose of azoxymethane, diamine oxidase activity was increased in the duodenum but was mainly inhibited in the colon. Intestinal diamine oxidase activity may then be influenced by regulatory processes induced by azoxymethane rather than by a direct effect.

Amine Oxidase (Copper-Containing)↗
PubMed2006

Nitric oxide-releasing aspirin and indomethacin are potent inhibitors against colon cancer in azoxymethane-treated rats: effects on molecular targets.

Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAID) are promising chemoprevention agents; unlike conventional NSAIDs, they seem free of appreciable adverse effects, while they retain beneficial activities of their parent compounds. Their effect on colon carcinogenesis using carcinoma formation as an end point is unknown. We assessed the chemopreventive properties of NO-indomethacin (NCX 530) and NO-aspirin (NCX 4016) against azoxymethane-induced colon cancer. Seven-week-old male F344 rats were fed control diet, and 1 week later, rats received two weekly s.c. injections of azoxymethane (15 mg/kg body weight). Two weeks after azoxymethane treatment, rats (48 per group) were fed experimental diets containing NO-indomethacin (0, 40, or 80 ppm), or NO-aspirin (1,500 or 3,000 ppm), representing 40% and 80% of the maximum tolerated dose. All rats were killed 48 weeks after azoxymethane treatment and assessed for colon tumor efficacy and molecular changes in colonic tumors and normally appearing colonic mucosa of different dietary groups. Our results suggest that NO-indomethacin at 40 and 80 ppm and NO-aspirin at 3,000 ppm significantly suppressed both tumor incidence (P < 0.01) and multiplicity (P < 0.001). The degree of inhibition was more pronounced with NO-indomethacin at both dose levels (72% and 76% inhibition) than with NO-aspirin (43% and 67%). NO-indomethacin at 40 and 80 ppm and NO-aspirin at 3,000 ppm significantly inhibited the colon tumors' (P < 0.01 to P < 0.001) total cyclooxygenase (COX), including COX-2 activity (52-75% inhibition) and formation of prostaglandin E2 (PGE2), PGF2alpha, and 6-keto-PGF1alpha, and TxB2 from arachidonic acid (53-77% inhibition). Nitric oxide synthase 2 (NOS-2) activity and beta-catenin expression were suppressed in animals given NO-NSAID. In colonic crypts and tumors of animals fed these two NO-NSAIDs, there was a significant decrease in proliferating cell nuclear antigen labeling when compared with animals fed the control diet. The results of this study provide strong evidence that NO-NSAIDs possess strong inhibitory effect against colon carcinogenesis; their effect is associated with suppression of COX and NOS-2 activities and beta-catenin levels in colon tumors. These results pave the way for the rational design of human clinical trials.

Acetates↗
PubMed1992

Association between permeability of the colonic wall and azoxymethane induced cancer of the colon in rats.

OBJECTIVE: To investigate the association between colonic permeability and the development of azoxymethane induced colonic cancer in rats. MATERIAL: Seventy-three male Fischer-Cooper hybrid rats. INTERVENTIONS: Measurement of the concentrations of sodium fluorescein in plasma as an indication of its passage across the bowel wall in control rats, and six weeks and six months after injection of azoxymethane. RESULTS: Forty-seven rats were given azoxymethane, and 26 acted as controls. Sodium fluorescein was instilled into segments of right (n = 46) and left (n = 27) colon and measured in peripheral blood; significantly higher concentrations were recorded after instillation into the left than into the right colon. No tumours developed in the 15 rats that were given azoxymethane and were examined after six weeks. At six months, however, 29 of the remaining 32 had developed 94 macroscopic tumours (range 1-12 tumours/rat), and 89 of these (95%) were in the left colon. CONCLUSION: The greater permeability of the left colon in rats compared with the right may be associated with the higher incidence of carcinomas in the left compared with the right colon.

Animals↗
PubMed2004

Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells.

Trigonella foenum graecum (fenugreek) is traditionally used to treat disorders such as diabetes, high cholesterol, wounds, inflammation, and gastrointestinal ailments. Recent studies suggest that fenugreek and its active constituents may possess anticarcinogenic potential. We evaluated the preventive efficacy of dietary fenugreek seed and its major steroidal saponin constituent, diosgenin, on azoxymethane-induced rat colon carcinogenesis during initiation and promotion stages. Preneoplastic colonic lesions or aberrant crypt foci (ACF) were chosen as end points. In addition, we assessed the mechanism of tumor growth inhibition of diosgenin in HT-29 human colon cancer cells. To evaluate the effect of the test agent during the initiation and postinitiation stages, 7-week-old male F344 rats were fed experimental diets containing 0% or 1% fenugreek seed powder (FSP) or 0.05% or 0.1% diosgenin for 1 week and were injected with azoxymethane (15 mg/kg body weight). Effects during the promotional stage were studied by feeding 1% FSP or 0.1% diosgenin 4 weeks after the azoxymethane injections. Rats were sacrificed 8 weeks after azoxymethane injection, and their colons were evaluated for ACF. We found that, by comparison with control, continuous feeding of 1% FSP and 0.05% and 0.1% diosgenin suppressed total colonic ACF up to 32%, 24%, and 42%, respectively (P < or = 0.001 to 0.0001). Dietary FSP at 1% and diosgenin at 0.1% fed only during the promotional stage also inhibited total ACF up to 33% (P < or = 0.001) and 39% (P < or = 0.0001), respectively. Importantly, continuous feeding of 1% FSP or 0.05% or 0.1% diosgenin reduced the number of multicrypt foci by 38%, 20%, and 36% by comparison with the control assay (P < or = 0.001). In addition, 1% FSP or 0.1% diosgenin fed during the promotional stage caused a significant reduction (P < or = 0.001) of multicrypt foci compared with control. Dietary diosgenin at 0.1% and 0.05% inhibited total colonic ACF and multicrypt foci formation in a dose-dependent manner. Results from the in vitro experiments indicated that diosgenin inhibits cell growth and induces apoptosis in the HT-29 human colon cancer cell line in a dose-dependent manner. Furthermore, diosgenin induced apoptosis in HT-29 cells at least in part by inhibition of bcl-2 and by induction of caspase-3 protein expression. On the basis of these findings, the fenugreek constituent diosgenin seems to have potential as a novel colon cancer preventive agent.

Animals↗
PubMed1978

Promotion of azoxymethane-induced colonic neoplasia by resection of the proximal small bowel.

Potential enhancement of intestinal neoplasia by compensatory mucosal hyperplasia was tested in rats subjected to 50% proximal small bowel resection (PSBR) 10 days after the last of 16 weekly injections of azoxymethane. Azoxymethane alone increased jejunal contents of RNA and DNA each by 26% at 17 to 18 weeks (p less than 0.01) before there was macroscopic evidence of neoplasia. Three months after PSBR alone, ileal hyperplasia was characterized by increased amounts of RNA (42 to 76%) and DNA (68 to 95%), taller villi, deeper crypts, and luminal dilation (p less than 0.05 to 0.001); however, the colon showed only patchy hyperplasia. When the combined effects of azoxymethane and PSBR were observed 26 to 30 weeks after the first injection, rats with PSBR had an increased number of colonic tumors per animal (2.9 versus 1.6 for controls; p less than 0.02). Despite the intense ileal hyperplasia produced by PSBR, ileal neoplasia did not occur. Enhanced colonic carcinogenesis followed sequential exposure of the mucosa to the carcinogen (azoxymethane) and to the promoting factor (PSBR).

Adaptation, Physiological↗
PubMed1995

Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and human colon cancer cell lines.

Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells. Azoxymethane-induced rat colon tumors display many features of the human disease, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. We have prepared monoclonal antibodies to a microsomal fraction isolated from an azoxymethane-induced rat colon tumor and selected an antibody that detects cancer-associated changes. Monoclonal antibody (mAb) 3A7 recognizes a determinant on type 2 chain blood group A (GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) and B (Gal alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) oligosaccharides. Expression of the epitope detected by this antibody was developmentally regulated in rat colon, with maximal expression from day 4-21 after birth. Immunohistochemical staining and Western blotting analyses of azoxymethane-induced colon tumors revealed increased expression of the epitope in all of the 21 colonic tumors examined, including preneoplastic glands within transitional mucosa. Conventional and signet-ring adenocarcinomas that had invaded through the muscularis propria (Duke's B2) consistently showed the most intense staining with mAb 3A7, including regions depicting angioinvasion. Some of the lymph node metastases (Duke's C2) stained poorly with the antibody. The epitope was also expressed in blood group A positive human colon carcinoma cell lines, including HT29 and SW480 but not by SW620, a cell line derived from a lymph node metastasis isolated in vivo from the SW480 primary tumor, or in the blood group B cell line SW1417. The glycoproteins detected by mAb 3A7 in rat colon tumors and HT29 cells ranged in size between 50 and 200 kd, including a major species of 140 kd. Affinity chromatography of detergent lysates of normal rat colon on the blood group A specific lectin Dolichos biflorus (DBA)-agarose resulted in nearly quantitative binding of glycoprotein species detected by the antibody. By contrast, immunoreactive glycoproteins from rat colon tumors or HT29 cells bound poorly to DBA-agarose but were retained by another blood group A-binding lectin, Helix-pomatia (HPA)-agarose. These results indicate that colon carcinogenesis results in quantitative as well as qualitative changes in oligosaccharides detected by mAb 3A7 and suggest that the combined use of mAb 3A7 and blood group A-specific lectins may provide a useful tool for early detection of colon cancer.

ABO Blood-Group System↗
PubMed1992

Inhibitory effect of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid, on azoxymethane-induced intestinal carcinogenesis in rats.

Modifying effects of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel synthesized retinoid (KYN-54), on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of ninety male F344 rats, 6 weeks old, were divided into 4 groups. Group 1 (20 rats) was fed a diet containing KYN-54 at a concentration of 0.02% for 3 weeks, during which time 2 s.c. injections of azoxymethane (15 mg/kg) were applied and then kept on a basal diet until the end of the experiment (1 year). Group 2 (30 rats) was given azoxymethane as in group 1 and fed the basal diet throughout, without synthetic retinoid exposure. Group 3 (20 rats) was administered KYN-54 at the commencement of the experiment, but not given the carcinogen. Group 4 (20 rats) received a basal diet alone throughout the experiment and served as a control. Intestinal tumors were seen in groups 1 and 2, their incidence and average number in group 1 (74%, 1.07 +/- 0.87) being significantly less than in group 2 (39%, 0.56 +/- 0.78) (P < 0.02 and P < 0.05, respectively). These results suggest that the synthetic retinoid might be a promising chemopreventive agent for intestinal neoplasia.

4-Butyrolactone↗
PubMed2005

Induction by lysophosphatidic acid of peritoneal and pleural metastases of intestinal cancers induced by azoxymethane in Wistar rats.

The effects of 1-oleoyl lysophosphatidic acid on the induction of metastasis from intestinal adenocarcinomas induced in rats by azoxymethane and on RhoA activity in the tumors were investigated in male Wistar rats. Rats were given a weekly s.c. injection of azoxymethane (7.4 mg/kg body weight) for 10 weeks and, from week 16, s.c. injection of lysophosphatidic acid (5 or 15 microg/kg body weight) every other day until the end of the experiment in week 45. Lysophosphatidic acid at both dosages significantly increased the incidence of peritoneal metastasis. Its administration at higher dosage also significantly enhanced the development of pleural metastasis. Although lysophosphatidic acid at both dosages had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors, its administration at both dosages significantly increased the incidence of vessel invasion of adenocarcinomas. Lysophosphatidic acid also increased the activity of RhoA in the tumors, but not the cellular proliferation and vascularity of the colon tumors. Our findings indicate that lysophosphatidic acid significantly increased the incidence of peritoneal and/or pleural metastases from intestinal adenocarcinomas induced in rats by azoxymethane through RhoA activation.

Adenocarcinoma↗