Colonic cancer induced by 1,2-dimethylhydrazine (DMH) in rats after partial colectomy

Using colonic cancer induced by DMH as experimental model, carcinogenic rate in the rats with or without partial colectomy was compared in order to study the etiology of the local recurrence of large bowel cancer after radical resection and observe the influence of operative injury on carcinogenesis. Sixty five male Wistar rats were divided into two groups: 48 with a partial colectomy (group 1) and 17 controls (group 2). All were given subcutaneous injection of DMH 20 mg/kg weekly for twenty weeks. Then, some rats were killed on scheduled time, the others were sacrificed in the 29th week. The results showed that carcinogenic rate was 87.5% and 58.8% in groups 1 and 2 (P less than 0.05). The tumor number in anastomotic site in group 1 (57.1%) was much higher than that at corresponding site in group 2 (28.6%) (P less than 0.05). It is suggested that the trauma itself be one of the promoting factors for cancer recurrence in addition to implantation during operation, residual tumor, etc. Large bowel cancer induced by DMH in rats may be used as an experimental model in studying the same cancer in the human being. Furthermore, after having given DMH, large bowel cancer incidence of the rats in different intervals is described.     

Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet

To examine the influence of hypercholesteremia on 1,2-dimethylhydrazine (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary cholesterol (CH, 0–2%) and cholic acid (CA, 0.25%) with or without DMH (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary cholesterol and cholic acid all significantly increased total serum cholesterol and lipids but only a high cholesterol diet (2% CH plus 0.25% CA) decreased the activity of glutathione peroxidase (GSH-Px) and increased the formation of peroxides in the colon (P < 0.01). The rats that received the combination of DMH and high cholesterol diet enhanced these effects. At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone. It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ.     

Colorectal carcinoma in a rat model: suppression of tumour development and altered host immune status following treatment with anti B-lymphocyte serum

The rate of colonic tumour development and immune capability in rats whose B-lymphocyte function was suppressed by injections of rabbit anti-rat IgM and also given the carcinogen dimethylhydrazine (DMH) were studied. Four rat groups were arranged to receive either DMH + anti-IgM, DMH + normal rabbit serum (NRS), saline + anti-IgM, or saline + NRS. Tumour weight, blood and mesenteric lymph node B-lymphocyte numbers, in vivo allograft response, in vitro lymphocytotoxicity, and leucocyte migration inhibition response (LMI) were recorded fortnightly. Tumour induction was delayed in the DMH + anti-IgM (treated tumour) group, which developed less tumour than the DMH + NRS (untreated tumour) group (p less than 0.001). Spleen cell lymphocytotoxicities were depressed in treated rats when compared to either the saline + anti-IgM (treated control) rats or the untreated rats (P less than 0.02), whereas anti-IgM treatment suppressed lymphocytotoxicity responses in control rats (p less than 0.05). The untreated tumour rats were tumour immune by LMI; however, the treated tumour rats did not express this in vitro tumour immunity. The B-lymphocyte levels in the mesenteric lymph nodes of untreated tumour rats increased with tumour induction (p less than 0.05), whereas in the treated tumour rats B-lymphocyte levels were not similarly stimulated.     

The effect of 1,2-dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the Wistar Furth rat

1,2-dimethylhydrazine (DMH)-induced colon cancer in Wistar/Furth (W/Fu) rats is analogous in many ways to human colorectal cancer. As part of our attempt to understand the immunobiology of these tumors, we have utilized the recently available monoclonal antibodies W3/25 and OX8 to monitor helper (Th) and suppressor (Ts) lymphocyte subpopulations. Normal untreated male W/Fu rats of less than 1 year of age were phenotyped (n = 43). The mean percentage of Th and Ts was 42 +/- 1 (mean +/- SEM) and 33 +/- 1, respectively. The mean Th/Ts ratio was 1.3 +/- 0.1. A Th/Ts equal to or greater than 1 is considered "normal" in the W/Fu rat. The DMH-treated rats (20 mg/kg/wk) were evaluated in initial experiments at various intervals after treatment. Rats studied 24 hours after a single DMH injection had no alterations in T cell subsets. Rats studied 28, 32, and 65 weeks after the start of 16 weekly DMH injections were found to have a decrease in the percentage of Th and a relative increase in Ts, with Th/Ts ratios of 0.6 +/- 0.2, 0.7 +/- 0.1, and 0.7 +/- 0.1, respectively (each P less than 0.01). In a separate experiment in which rats were studied after 4, 8, and 16 weeks of DMH injections, no alterations in T cell subsets were noted. Rats (n = 5) studied at 20 weeks after the start of DMH were found to have 41 +/- 3% Th and 36 +/- 2% Ts and a Th/Ts ratio of 1.2 +/- 0.1. Three of five rats were found to have adenocarcinomas. Four of five rats had Th/Ts less than 1. One rat with Th/Ts equal to 0.9 had metastatic disease. Rats studied at 25 weeks (n = 8) were found to have more advanced carcinomas (4/8) that were causing obstruction or bleeding in the animal. There was a significant decrease in Th and Ts in this group, with 24 +/- 3% and 26 +/- 3% respectively (P less than 0.001). The Th/Ts ratio for this group was 0.9 +/- 0.1 (P less than 0.01). In other experiments, rats were treated with DMH or placebo over a 16-week period and serially bled during and after treatment. No effect of DMH treatment on T cell subsets was noted. Repeated bleeding alone was noted to cause persistent alterations of T cell subpopulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Calcium inhibits colon carcinogenesis in an experimental model in the rat

Different dietary factors can affect colorectal cancer incidence. However, the effect of increased levels of dietary calcium on neoplasms is unclear. The present study was designed to examine the effect of a low calcium supplement on experimental colon carcinogenesis induced by parenteral administration of dimethylhydrazine (DMH). One hundred and twenty 10-week-old Sprague-Dawley rats were divided into five groups of equal sex distribution. The 10 rats in group A (control group) received no treatment; the 30 rats in group B (DMH group) were injected subcutaneously with 18 weekly doses of 21 mg/kg DMH; the 20 rats in group C (EDTA control group) received EDTA solution only; the 30 rats in group D (calcium group) received calcium at 3.2 g/l by adding calcium lactate to the drinking water from the start until the conclusion of the experiment; and the 30 rats in group E (DMH + calcium group) received oral calcium supplements at the same dose as the rats in group D (calcium group) and the same DMH injections as the rats in group B (DMH group). The rats were sacrificed at 25-34 weeks. In group E, we observed a significant diminution in the number of tumours (P = 0.01); an increase in the number of tumour-free animals (P = 0.006); a change in tumour location towards the distal colon (P < 0.025); more adenomas (P = 0.02); and a diminution of adenocarcinomas and mucinous carcinomas, although this was not significant. We conclude that a low dietary calcium supplement in rats inhibits colon cancer carcinogenesis induced by DMH, and changes tumour location towards the distal colon.     

Plasma lipids and prolactin in patients with breast cancer

In a comparative study of pre- and postmenopausal women with benign and malignant breast disease, a number of differences were observed in circulating plasma prolactin and lipid concentrations. Plasma lipids, phospholipids, triglycerides, cholesterol and free fatty acids were all higher in blood obtained from breast cancer patients prior to surgery. HDL-Cholesterol levels were significantly lower in these patients. These differences remained when the patient groups were sub-divided according to menopausal status. Plasma prolactin concentrations were also found to be higher in cancer compared with non-cancer patients, this effect being more marked in premenopausal than in postmenopausal patients. Premenopausal patients with invasive or poorly differentiated disease had significantly higher prolactin levels than those with non-invasive disease. No correlations were found between plasma prolactin and any of the lipid fractions.     

Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats

BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n = 30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects.     

Lipids status in human breast cyst fluids

Benign mammary gross cystic disease is the most common breast lesion; women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal population. Total cholesterol, high- and low-density lipoproteins fractions, triglycerides and phospholipids, lipase activity and total lipid concentrations were measured in cyst fluids and sera from 89 women affected by gross cystic breast disease. Total cholesterol and high-density lipoprotein content were significantly (P<0.001) greater in pooled cyst fluids than normal sera. Moreover, data analyses show a significant increase in the mean values of total lipids and lipase activity in metabolically active apocrine cysts, when compared to the flattened cysts (P<0.001). The lipids feature of apocrine cysts could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface glycolipid and steroidogenic metabolism and may provide further knowledge about the functional stage changes of gross breast cysts.     

Uptake of plasma lipids by tissue-isolated hepatomas 7288CTC and 7777 in vivo.

The uptake of myristic (C14:0), palmitic (C16:0), palmitoleic (C:16,N-7), stearic (C18:0), oleic (C18:1,N-9), linoleic (C18:2,N-6) and arachidonic (C20:4,N-6) acids from plasma free fatty acids (FFA), triglycerides (TGA), phospholipids (PL) and cholesterol esters (CE) was measured in tissue-isolated hepatomas 7288CTC and 7777 in vivo. Adult tumour-bearing Buffalo rats were fed a normal chow diet ad libitum and were subjected to darkness from 1800 to 0600 h. Arterial plasma levels of FFA, TGA, PL and CE were increased during the dark period without change in fatty acid compositions. Arteriovenous difference measurements of tumour lipid uptake were performed between 0600 and 0900 h and included both high (dark) and low (light) arterial blood lipid concentrations. The rate of lipid uptake from each lipid class was directly dependent on the rate of supply of the lipid to the tumour. The efficiency of uptake, however, depended on the type of plasma lipid and the tumour. During one pass of arterial blood, hepatoma 7288CTC (n = 5 to 13) removed 46, 33, 36 and 31%, and hepatoma 7777 (n = 7 to 9) removed 48, 50, 52 and 49% of the fatty acids supplied in FFA, TGA, PL and CE, respectively. Perfusion of tissue-isolated tumours in situ with donor blood containing plasma free (1-14C)palmitic acid showed that 14C-palmitic acid was removed from the arterial blood and was incorporated into tumour lipids and that 14CO2 was released into the tumour venous blood. Uptake of the seven fatty acids over a 24 h period was greatest from PL greater than TGA greater than FFA greater than CE and was estimated to total 18.1 +/- 3.5 mg fatty acids g-1 for hepatoma 7288CTC and 25.9 +/- 3.5 mg fatty acids g-1 for hepatoma 7777. Both hepatoma 7288CTC and 7777 grew at a rate of about 1 g day-1 and contained 13.4 +/- 2.5 and 10.6 +/- 3.9 mg of these 7 fatty acids g-1 tumour wet weight, respectively. We conclude that these two tumours obtain all of the fatty acids needed for daily growth from host arterial blood.     

Effects of dietary N-3 and saturated fats on growth rates of the human colonic cancer cell lines SW-620 and LS 174T in vivo in relation to tissue and plasma lipids

Ninety nude mice were inoculated subcutaneously with 1 x 10(7) cells of the human colonic cancer cell lines, SW-620 and LS174T. Tumour growth was assessed weekly for three weeks whilst the animals were receiving one of three diets: control (4.6% fat), coconut (20% fat, saturated fatty acids) and Maxepa (20% fat; n-3 fatty acids). At the end of the study SW-620 tumour weights (mean +/- SD, gm) were: control = 0.38 +/- 0.22, coconut = 0.43 +/- 0.31, Maxepa 0.20 +/- 0.16; the LS174T tumour weights were control = 1.33 +/- 1.27, coconut = 0.47 +/- 0.74, Maxepa = 0.38 +/- 0.56 (p less than 0.001, analysis of covariance). The Maxepa diet produced significant retardation in tumour growth (p less than 0.001). This was associated with reduced levels of linoleic acid and arachidonic acid in adipose tissue and tumour lipids with incorporation of n-3 fatty acids (all p less than 0.01 at least, analysis of variance). Moreover, the Maxepa diet produced significant reductions of plasma cholesterol, phospholipids and triglycerides (all p less than 0.01).     

Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer.

We evaluated total plasma fatty acid concentrations and percentages, and the fatty acid profiles for the different plasma lipid fractions and red blood cell lipids, in 17 patients with untreated colorectal cancer and 12 age-matched controls with no malignant diseases, from the same geographical area. Cancer patients had significantly lower total plasma concentrations of saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives than healthy controls; when the values were expressed as relative percentages, cancer patients had significantly higher proportions of oleic acid and lower levels of linoleic acid than controls. With regard to lipid fractions, cancer patients had higher proportions of oleic acid in plasma phospholipids, triglycerides and cholesterol esters, and lower percentages of linoleic acid and its derivatives. On the other hand, alpha-linolenic acid was significantly lower in triglycerides from cancer patients and tended to be lower in phospholipids. Its derivatives also tended to be lower in phospholipids and triglycerides from cancer patients. Our findings suggest that colorectal cancer patients present abnormalities in plasma and red blood cell fatty acid profiles characterized by lower amounts of most saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives, especially members of the n-6 series, than their healthy age-matched counterparts. These changes are probably due to metabolic changes caused by the illness per se but not to malnutrition.     

Lipid metabolism in cancer cachexia.

The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation of [1-14C]triolein administered by intragastric intubation was significantly (P less than 0.05) higher in animals bearing the MAC16 tumour than in either non tumour-bearing controls or in animals bearing the MAC13 tumour. Intestinal absorption of [14C]lipid was significantly (P less than 0.05) reduced in animals bearing the MAC13 tumour when compared with either non tumour-bearing animals or MAC16 tumour-bearing animals, but was not significantly different in the latter two groups. The level of labelled lipids in heart and adipose tissue after an oral [14C]lipid load was significantly lower in animals bearing the MAC16 tumour compared with the other two groups. The level of tumour lipids was also higher in the MAC16 than in the MAC13 tumour after both an oral [14C]lipid load or by direct injection of [U-14C]palmitate complexed to albumin into epididymal fat pads. Oxidation of [U-14C]palmitate was also significantly enhanced in liver and heart homogenates from animals bearing the MAC16 tumour. These results suggest that in cachectic tumour-bearing animals mobilisation of body lipids is accompanied by an increased utilisation.     

Correlation of neomycin, faecal neutral and acid sterols with colon carcinogenesis in rats.

High fat diets have been implicated in incidence of colon cancer both in epidemiological and animal studies. Present investigation deals with the incidence, location and numbers of large and small bowel tumours induced by 1,2-dimethyl hydrazine (DMH) in rats fed high fat diets and neomycin. Neomycin was used to modify the faecal sterol metabolism and the relationship of the high fat diet and faecal neutral and acid sterols to the large bowel tumorigenesis was evaluated. DMH administered rats were fed with (a) 20% safflower oil; (b) 20% safflower oil and neomycin; (c) 20% safflower oil, cholesterol and cholic acid; and (d) 20% safflower oil, cholesterol, cholic acid and neomycin. Neomycin was found to be associated with both increase and decrease of tumour numbers. The faecal sterols lithocholic and deoxycholic acids were found to have no participation, while cholesterol and cholic acid were found to decrease with increase in tumour numbers. However, faecal coprostanol has been found to have a significant positive correlation with tumorigenesis in all dietary groups. Therefore coprostanol might possibly be associated with colon carcinogenesis in DMH-fed rats and cholesterol metabolism in gut appears to be related to the development of tumours.     

Detailed faecal bile acid profile: a diagnostic test for colorectal cancer?

Detailed profiles of bile acids in faeces were evaluated as a diagnostic test for colorectal cancer in rats. Twenty-seven bile acid peaks were measured using improved methods of extraction and separation followed by the sensitive and specific techniques of capillary column gas liquid chromatography and mass spectrometry. Colorectal cancer was induced in experimental animals (female Sprague-Dawley rats, n = 20) by subcutaneous injection of dimethylhydrazine (DMH) and faecal unconjugated bile acids compared with those in the control group (n = 20). The amount of total faecal unconjugated bile acids was lower in the animals administered DMH (255 mg/day vs 334 mg/day: (P = 0.04), and the excretion of seven individual bile acids was reduced when compared with those in the control group (P less than 0.01). In order to use the faecal bile acid profiles as a diagnostic test, linear discriminant analysis was performed. A discriminant score was derived which was applied to each profile, to determine to which group (control or DMH) each animal belonged retrospectively. All analyses were performed blind, and 90% of the animals were correctly assigned. In man, as in rats, the bile acid profile of faces is equally complex and the bile acid profile may be useful as a diagnostic test.     

Aminoglutethimide-induced dyslipidemia. Experimental study

Aminoglutethimide (AG) is a drug that inhibits steroid synthesis; it is used in advanced breast cancer. After the observation of abnormalities in lipid metabolism in patients, we realized an experimental study to try to look for a pathogenetic hypothesis. Three groups of rats received respectively AG, Hydrocortisone (HC) or both (AG + HC) and were compared to controls. Animals treated with AG (with or without HC) had a greater liver content of triglycerides, cholesterol and phospholipids than controls. Cholesterol plasma level was higher in animals treated with AG + HC. The bile flow was higher in rats receiving AG and AG + HC whereas biliary salt concentrations were lower. These variations could be the consequence of both an enzymatic induction and an inhibition of some cytochrome P450 dependent hydroxylases.     

Enhanced thyroid carcinogenicity of N-nitrosobis(2-oxopropyl)amine in Otsuka Long-Evans Tokushima Fatty rats, a model of type II diabetes mellitus

Epidemiologic data suggest that diabetes mellitus type II is a risk factor for several types of cancer, including pancreatic, liver, colon and thyroid cancers. In the present study, effects of diabetes/hyperlipidemia on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cancer development were examined in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, model animals for non-insulin-dependent diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats, appropriate controls. Males of both strains were given four subcutaneous injections of BOP (10 mg/kg body wt) or saline on alternative days, starting at 5 weeks of age. BOP induced tumors in a variety of tissues, including the thyroid gland, colon, kidney, liver and lung. The highest yields were noted for thyroid tumors, the incidence (P = 0.0182) and multiplicity (P < 0.001) of BOP-induced thyroid cancers with marked fibrosis being significantly higher in OLETF than in LETO rats. Interestingly, anaplastic thyroid carcinomas were observed limited to the BOP-treated OLETF rats. Additionally, a greater incidence and frequency of aberrant crypt foci, putative precursor lesions for colon tumors, was observed in the BOP-treated OLETF group. However, BOP was ineffective at inducing pancreatic ductal tumors. No thyroid, liver, lung or colon tumors were found in the OLETF and LETO rats receiving the vehicle. Significant increases in serum levels of insulin, glucose, phospholipids, triglycerides and total cholesterol were detected in the OLETF rats compared with the LETO rats, regardless of the treatment. Our results indicate that diabetic/hyperlipidemic state can enhance BOP-induced carcinogenesis of the thyroid gland and to a lesser extent the colon in OLETF rats.     

Serum lipids and endometrial cancer risk: Results from the HUNT‐II study

Obesity is a major risk factor for endometrial cancer. Still, the association of obesity‐related metabolic factors, such as serum lipids and lipoprotein levels, is unclear. We prospectively examined the association of serum levels of triglycerides, total cholesterol, low‐density lipoprotein cholesterol, non–high‐density lipoprotein (non‐HDL), and HDL cholesterol with endometrial cancer risk among 31,473 women. During 9 years of follow‐up, 100 cases of endometrial cancer were identified by linkage to the Cancer Registry of Norway. There was a positive association of serum triglyceride levels with endometrial cancer risk. Comparing the highest to the lowest quartile of triglycerides, the age‐adjusted hazard ratio was 2.34 (95% CI: 1.04–5.28), and further adjustment for body mass index attenuated the association (hazard ratio 1.79, 95% CI: 0.79–4.05). For total serum cholesterol, low‐density lipoprotein cholesterol and HDL cholesterol there were no associations with endometrial cancer risk, either without or after adjustment for body mass index. Serum triglyceride levels were positively associated with the risk of endometrial cancer, and some of the association seems to be attributable to obesity. Apart from higher estrogen levels produced in adipose tissue, mechanisms more specifically related to triglycerides may also be involved in endometrial cancer. Further prospective studies on this subject are needed to better understand the association of blood lipids with endometrial cancer risk. © 2009 UICC     

Splanchnic blood flow changes in the presence of hepatic tumour: evidence of a humoral mediator.

Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-1 min, s.e. 21.5, vs 51.7 mmHg ml-1 min, s.e. 7.4, P < 0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases.     

The effects of cholic acid and bile salt binding agents on 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat

The theory that bile salts may be colon tumour promoters wastested in the dimethylhydrazine (DMH)-induced rat colon cancermodel. Fifty Wistar rats were randomly allocated to one of fiveexperimental groups (n = 10), all fed the same standard diet.One group served as saline-injected controls, while the otherfour groups received DMH (20 mg/kg body weight/rat/week s.c.)for 20 weeks. In addition, each of the DMH-injected groups concurrentlyreceived 20 weekly i.g. instillations of one of the following:cholic acid (a bile acid); cholestyramine or aluminium hydroxide(both bile acid binding agents), or water. After a years observationperiod, all the controls were alive and tumour-free, while allthe DMH-injected rats had died of histologically proven coloncancer. Irrespective of the type of gastric instillate, therewere no significant differences between the groups in termsof time to tumour presentation, survival, in the necropsy incidenceof primary or metastatic colon cancer, or in the numbers ofcolon tumours per group. The data suggest that bile salts andbile salt binding agents are not colon tumour promoters in therat. The bile salt theory of colon carcinogenesis may need reappraisal.