QUALITATIVE STUDY OF SIALOMUCINS CHANGES DURING N－METHYL－N－NITROSOUREA－INDUCED C OLONIC CARCINOGENESIS IN MICE

ＱＵＡＬＩＴＡＴＩＶＥＳＴＵＤＹＯＦＳＩＡＬＯＭＵＣＩＮＳＣＨＡＮＧＥＳＤＵＲＩＮＧＮ－ＭＥＴＨＹＬ－Ｎ－ＮＩＴＲＯＳＯＵＲＥＡ－ＩＮＤＵＣＥＤＣＯＬＯＮＩＣＣＡＲＣＩＮＯＧＥＮＥＳＩＳＩＮＭＩＣＥＷａｎｇＱｉａｎｇ王强；ＷａｎｇＹｕａｎｈｅ王元和；...     

The mucin profile in the mucosa of the large intestine in neoplasms]

Qualitative and quantitative changes in secretion of goblet cells of large bowel mucosa in adenomatous polyps (60), adenocarcinoma (30) and bioptates of adjacent transitional mucosa (30) were studied. As neoplasia progressed, mucin profile appeared to follow a certain pattern: it reached its peak in moderate dysplasia in polyps containing predominantly sulphomucins; subsequently both sulphomucin and sialomucin levels decreased. Adenocarcinomas showed a sharp drop in glycoprotein level, and an insignificant build-up of sialomucins was registered in some cases only. Enhanced abnormal secretion was observed in mucinous carcinoma and adenocarcinoma characterized by the presence of large mucinous areas. Also, qualitative changes were identified in transitional mucosa adjacent to tumor.     

Detection of the tumor-associated glycoprotein antigen (TAG-72) in premalignant lesions of the colon

We used monoclonal antibody B72.3 to study the expression of the colorectal carcinoma-associated antigen TAG-72 in premalignant colonic lesions with the immunoperoxidase technique. This antigen, which is rarely detectable in the normal colonic epithelium, was expressed in 13 of 19 adenomas with moderate to severe dysplasia and nine of nine cases of inflammatory bowel disease. The antibody reacted with the normal-appearing mucosa adjacent to a carcinoma in 10 of 12 cases, although only eight of the tumors expressed the antigen. The expression of the TAG-72 antigen in the colonic epithelium may be an early marker of malignant transformation.     

Expression of cloned sequences in biopsies of human colonic tissue and in colonic carcinoma cells induced to differentiate in vitro

A computer-based scanning and image-processing system has been developed to quantitate the relative level of expression of each of 4000 cloned complementary DNA sequences in small biopsies routinely removed from the mucosa of normal and neoplastic human large intestine. Individuals have been studied from well-defined population groups in which colonic epithelial cells have progressed to increasingly advanced stages of neoplastic transformation. Comparison of normal colonic mucosa to colonic carcinomas demonstrated alterations in expression of approximately 7% of the cloned sequences; fewer changes were found between benign colonic adenomas and either normal colonic mucosa or carcinomas. A subset of the sequences which change in expression during progression from normal mucosa, to adenoma, to carcinoma showed complementary changes when colon carcinoma cells were induced to differentiate in vitro with sodium butyrate; quantitative correlations between in vivo and in vitro results were highly significant. Comparison of normal colonic mucosa with mucosa from patients with the autosomal dominant disease familial polyposis revealed more extensive alterations in gene expression involving approximately 25% of the clones screened. Flat colonic mucosa in familial polyposis is therefore markedly aberrant and may be highly dedifferentiated, suggesting several possible mechanisms for the very high incidence of cancer that develops in this epithelium.     

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats.

We have measured mitotic indices and 3H-thymidine-labelling indices for the colonic epithelial tumours induced in rats by the administration of dimethyl-hydrazine (DMH). The fraction-of-labelled-mitoses (FLM) technique has been used to estimate the duration of the cell-cycle phases. In general, mitotic and labelling indices in the tumours are similar to those in the proliferation zone of the normal crypt epithelium; lesions considered to be least well differentiated on histological grounds appear to have the lowest mean labelling index. Benign tumours and the different types of malignant tumours have mean cell-cycle times about half those of the normal mucosa.     

Effects of Imbalance of Apoptosis and Proliferation on Large Bowel Carcinogenesis in Mice

OBJECTIVE To observe the pattern of changes in the proliferation and apoptosis at different stages of large bowel carcinoma in mice, and to explore the effects of the imbalance of apoptosis and proliferation at different stages of large-intestine carcinogenesis.METHODS An experimental animal model for large intestine carcinogenesis of KUNMING-strain mice was used. The carcinomas were induced by subcuteneous injection of dimethylhydrazine (DMH) and the distribution and density changes of proliferating and apoptotic cells observed through multistages toward cancer formation. The animals were killed in groups at the 12th, 18th, 24th,and 32nd weeks of carcinoma induction. The apoptotic and proliferating cells were labeled separately using TUNEL and PCNA immunohistochemical staining methodsRF, RESULTS In the normal mouse mucosa, all the apoptotic cells were situated in the superficial layers, however, the proliferating cells were situated in the basement layers, and the amount of both were small. In the early stage of carcinoma induction, the proliferation and the apoptotic cells slightly increased in amount, but there were no obvious changes in their ratio. In the medium stage, the densities of both distinctly increased, but there were no obvious changes in the ratio. In the late stage, the densities of the proliferating and the apoptotic cells in the non-carcinoma mucosa were higher than those at other stages. The proliferating cells in the dysplastic mucosa increased progressively with the increasing degree of the lesions. Although the apoptotic cells increased, their changes did not occur with the degree of the lesions. Their ratio showed a decreasing tendency with the degree of the lesions.CONCLUSIONS (①The presence of an imbalance between cell proliferation and apoptosis was confirmed in the course of large intestine carcinogenesis in a mouse model. ②In the early stage of carcinoma induction both proliferation and apoptosis were at a low level; in the medium stage, they were both at a high level; and in the late stage (that is in carcinoma), proliferation was at a very high level, while apoptosis was at a low level. ③The proliferating cells increased progressively with the degree of dysplasia. There were no obvious changes in the apoptotic cells and their ratio to the proliferating cell sshowed a progressively increasing tendency. ④In the stage of cancer formation, the most essential change was the excessive decrease in the ratio of apoptosis to proliferation. These results support the hypothesis of “Cell Selective Proliferation“, which was raised by authors previously in a study on human large bowel carcinoma.     

Frequency of proliferation,apoptosis, and their ratio during rat colon carcinogenesis and their characteristic pattern in the dimethylhydrazine-induced colon adenoma and carcinoma

The imbalance between the cell proliferation and cell loss plays a crucial role in the carcinogenesis and tumor progression. However, the direction of these changes is still the matter of discussion. Thus, the aim of this study was to evaluate the proliferative activity, apoptotic activity, and proliferation/apoptosis ratio (P/A) assessed every 6 weeks in the colonic epithelium during 21 weeks of dimethylhydrazine (DMH) treatment in male Wistar rats. Moreover, it is necessary to answer the question whether these analyzed parameters correlate with the grade of differentiation or dysplasia of the induced tumors. It was found that DMH administration enhanced the proliferation in week 12 and 18 when compared with week 6. The proliferation in the control group did not change during the study. Up to week 12 of the experiment, there were no statistically significant differences between proliferative activity in the control and DMH-treated groups. In week 18, the proliferation in DMH-treated group was higher than in the control group. At all time points of the study, the apoptotic activity in the DMH-treated groups was significantly higher than in controls and in both groups, they dropped during the study. In the control group, apoptotic activity decreased in week 18 and was lower in comparison to that in week 6 and 12. In the group treated with DMH, apoptosis dropped at week 12 and was lower than in week 6. The P/A ratio did not change during the study in the control group, but increased in the DMH-treated group. After 21 weeks of DMH administration, 28 cases of colon adenocarcinoma and nine cases of colon adenoma were obtained and classified according to the WHO classification (1989) for human colon tumors. The adenocarcinomas were divided into four groups: well, moderately, poorly differentiated, and signet-ring cell carcinoma. The colon adenomas were divided into three groups: adenoma with mild, moderate, and severe grade of dysplasia. The proliferative activity in signet-ring cell carcinoma was significantly smaller than in well, moderately, and poorly differentiated adenocarcinoma and apoptotic activity was smaller than in well-differentiated adenocarcinoma. A weak (statistically nonsignificant) negative correlation was also observed between the proliferative and apoptotic activity in adenocarcinoma or adenoma and their grade of dedifferentiation or dysplasia, respectively.     

Quantification of telomerase activity of regions unstained with iodine solution that surround oral squamous cell carcinoma

The aim of this study was to analyze the iodine-unstained region expanding around oral squamous cell carcinoma (SCC) by quantification of telomerase activity. The epithelial dysplasia often observed around SCC is considered to cause local recurrence or a second primary cancer. However these areas are hard to distinguish from normal mucosa. To clear the border of the expanding epithelial dysplasia around SCC, we stained with 3% iodine solution, and then decided the surgical margin. We measured quantification of telomerase activity in tumor, in epithelial dysplasia, and also in normal epithelium. Thirty-three primary cases of oral SCC which have iodine-unstained region around lesions were investigated. Fluorescense-based TRAP was applied to obtain quantification of telomerase activity. We obtained the following results: histological examination confirmed that every patient's unstained region consisted of various degrees of epithelial dysplasia. The quantified telomerase activities for squamous cell carcinoma, epithelial dysplasia and normal epithelium were 53.9, 39.6 and 2.7 U/microgP, respectively, and there was a significant difference between carcinoma and normal areas, and between dysplasia and normal epithelium. Therefore, these findings suggest that the areas of epithelial dysplasia unstained by iodine consist of cells that are nearly cancerous and excessively proliferative, and that epithelial dysplasia around SCC should be resected together with the tumor. Vital staining with iodine is useful for identifying epithelial dysplasia around SCC.     

Carcinogenesis of intestinal-type gastric cancer and colorectal cancer is commonly accompanied by expression of brain (fetal)-type glycogen phosphorylase.

Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the role of this molecule in the gastrointestinal carcinogenesis. The only isoform expressed in gastric cancer was brain-type GP (BGP) using polymerase chain reaction (PCR) analysis. The expression of BGP, oncogene products and proliferating cell nuclear antigen in the gastric and colorectal carcinomas, their premalignant lesions, and the normal mucosa were examined using 136 gastric and 96 colorectal surgically resected specimens, and 55 endoscopically resected colorectal adenomas. The BGP visualized by immunohistochemistry was commonly present in intestinal-type gastric (80.6%) and colorectal (83.3%) carcinomas, whereas no BGP expression was seen in the normal human gastric and large intestinal mucosa except in the BGP foci described below. IMs with BGP had close correlation with intestinal-type gastric carcinoma, and some of them coexpressed accumulated p53 protein. The expression of BGP during 'adenoma carcinoma sequence' (ACS) showed excellent correlation with the increased dysplasia and was found prior to p53 expression. Positive staining in overtly normal looking colonic mucosa (BGP foci) was observed mainly around carcinomas without any adenoma component, and frequent p53 mutation (41.2%) was detected in the BGP foci using PCR-single strand conformation polymorphism analysis. It is suggested that BGP is a novel biomarker for carcinogenesis in the intestinal-type gastric carcinoma and in both of the pathways of ACS and the 'de novo' colorectal carcinoma.     

热休克蛋白10在大肠癌发生发展中的表达及其意义

目的了解热休克蛋白10（HSP10）在正常大肠粘膜、腺瘤和腺癌中的表达,并探讨其与大肠癌发生发展的关系.方法应用免疫组化Envision二步法,观察HSP10在正常大肠粘膜、腺瘤和腺癌中的表达,并比较其间是否存在差异.结果 HSP10在大肠腺瘤、腺癌中的阳性表达程度高于正常大肠粘膜（P〈0.001）;HSP10在不同程度不典型增生的大肠腺瘤、不同分化程度与淋巴结转移状态大肠腺癌中呈阳性至强阳性表达,统计学分析结果表明差异无显著性意义（P〉0.05）.结论提示HSP10与大肠癌的发生发展有关,有可能成为检测大肠癌的早期诊断标志物;HSP10的表达与大肠腺瘤的不典型增生程度和大肠癌的分化程度、淋巴结转移状态无关.     

Classification of aberrant crypt foci and microadenomas in human colon.

Aberrant crypt foci (ACF) can be observed and quantified on the mucosal surface of formalin-fixed human colon resections after staining with methylene blue. To determine whether these ACF could be identified in fresh tissue, 10 colon resections were collected after surgery for colorectal cancer. Unfixed and fixed flat normal colonic mucosa from each colon were scored for ACF under a dissecting microscope after methylene blue staining. The number of ACF per cm2 and the average number of crypts per foci correlated highly in unfixed and fixed mucosa (r = 0.93 and 0.78, respectively). A significantly higher frequency of lesions was found in left-sided compared to right-sided colon resections. To determine whether the topographic features of the ACF gave an indication of the histological appearance, 68 specimens containing ACF or normal mucosa were examined histologically. The presence of slit-like lumen in the crypts of ACF on the mucosal surface correlated with the presence of dysplasia at histology, thus identifying microadenomas. These two observations suggest that the topographic classification of ACF in vivo could be used to distinguish microadenomas, a putative precursor lesion of colon cancer.     

热休克蛋白10在大肠癌的表达及其临床病理意义

目的研究热休克蛋白10(heat shock protein 10,HSP10)在大肠癌发生、发展过程中的表达规律,了解其与大肠癌临床病理特征和术后生存期的关系。方法应用免疫组化EnVision二步法,检测HSP10在大肠正常黏膜、腺瘤和腺癌中的表达,及其与临床病理表现和术后生存期的相关性。结果HSP10在大肠正常黏膜、腺瘤和腺癌中均有表达,在腺瘤、腺癌中的表达明显强于正常黏膜(P<0.001);HSP10的阳性表达与大肠癌患者的年龄、性别、肿瘤浸润深度、局部淋巴结转移、远处转移、临床分期、组织学分化程度等临床病理特征和术后生存期均无关。结论HSP10在大肠腺瘤和腺癌的高表达,提示可能与大肠癌的发生发展有关;HSP10的阳性表达与大肠癌的临床病理特征和术后生存期无关。     

热休克蛋白10在大肠癌的表达及其临床病理意义

Objective： To investigate the expression of heat shock protein 10 （HSPIO） during genesis and development of large bowel carcinoma and discuss the clinical significance about its expression. Methods： The expression of HSPIO was observed in specimens from normal colonic mucosa （NC）, colorectal adenomas （CA） and colorectal adenocarcinomas （CAC） by immunohistochemistry EnVisionTM. Its correlations to clinicopathologic features, as well as to postoperative survival time of large bowel carcinoma patients were analyzed. Results： The expression of HSPIO was common in normal colonic mucosa, colorectal adenomas and adenocarcinomas and more intensive in colorectal adenomas and adenocarcinomas than that in normal colonic mucosa （P 〈 0.001）. The positive expression of HSPIO had no correlation to clinicopathologic features, including age, gender, primary tumor, infiltrating of regional lymph node, metastasis, clinical stage and histopathology of large bowel carcinoma patients, as well as to their postoperative survival time. Conclusion： HSPIO was overexpressed in the early stage of colorectal adenocarcinoma suggesting that it could serve as an index for early diagnosis of large bowl carcinoma. The positive expression of HSPIO had no correlation to clinicopathologic features or postoperative survival time of large bowel carcinoma patients.     

Epithelial dysplasia of the rabbit colon induced by degraded carrageenan

Colonic mucosal lesions, characterized by crypt abscesses and mononuclear cell infiltration, which resemble human ulcerative colitis can be induced in rabbits by short-term (7 to 8 weeks) administration of carrageenan according to our method. In this study experimental epithelial dysplasia of the colon was induced by the p.o. administration of lambda-degraded carrageenan for a much longer period of time. Fifteen rabbits, sensitized i.m. with the same substance 1 week before, were subjected to 12 or 28 months of treatment with 1% carrageenan solution in drinking water. Histological examination disclosed chiefly mild inflammatory changes of the colonic mucosa in all animals and a focal but high-grade dysplasia (nonpolypoid) involving the mucosal epithelium in three of the five animals treated for 28 months. The present observations suggested that epithelial dysplasia of the colon may be caused in association with inflammation and that the pathological condition produced by us can be a useful model of carcinoma in situ possibly resulting from inflammation.     

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.     

Antigens of gastric and intestinal mucous cells in human colonic tumours.

Using immunofluorescence methods, 3 antisera respectively stain 3 groups of mucous cells of the human gastrointestinal tract, showing specific antigens for each group of cells. The antigens of the first group, the M1 antigens, were principally associated with columnar cells of the gastric epithelium, the M2 antigens with mucous cells of gastric and Brünner''s glands, and the M3 antigen with the goblet cells of the intestinal mucosa. The gastric M antigens normally detectable in stomach and duodenum (but not in colon) were expressed in certain colonic tumours (benign or malignant) and in adjacent mucosa. They are always present with the intestinal M3 antigen. In 100 colonic adenocarcinomas, the intestinal M3 antigen was found in 53 cases, gastric M1 antigens in 29 cases, and gastric M2 antigens in 10 cases, always with the two other M antigens. A good correlation could be established between the association of M antigens and the histological type of tumour.     

60例喉乳头状瘤人类乳头状瘤病毒感染分析

[目的]研究人类乳头状瘤病毒感染与喉乳头状瘤发生的关系。[方法]利用免疫组织化学、原位分子杂交及PCR检测60例喉乳头状瘤、15例喉鳞状非典型增生上皮和10例正常喉黏膜上皮中人类乳头状瘤病毒(HPV)16/18E6蛋白的表达。[结果]免疫组化显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16/18E6蛋白的阳性率分别为10.0%(1/10)、33.3%(5/15)和80.0%(48/60);瘤组织中HPV16/18E6蛋白的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16/18E6蛋白的阳性率亦明显高于正常喉黏膜(P<0.05)。原位杂交显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16/18E6DNA的阳性率分别为10.0%(1/10)、40.0%(6/15)和83.3%(50/60);瘤组织中HPV16/18E6DNA的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16/18E6DNA的阳性率亦明显高于正常喉黏膜(P<0.05)。PCR显示在正常喉黏膜、非典型增生上皮及喉乳头状瘤组织中HPV16的阳性率分别为10.0%(1/10)、46.7%(7/15)和86.7%(52/60);瘤组织中HPV16的阳性率明显高于非典型增生上皮和正常喉黏膜(P<0.05),非典型增生上皮中HPV16的阳性率亦明显高于正常喉黏膜(P<0.05)。[结论]高危型HPV16/18型感染可能在喉乳头状瘤的发生中起重要作用。     

Relationship between the Nature of Mucus and Crypt Multiplicity in Aberrant Crypt Foci in the Rat Colon

Aberrant crypt foci (ACF)induced in the distal colon of F344 male rats, 4, 8, 12 and 35 weeks after the first administration of 1, 2-dimethylhydrazine-2HCl (DMH) were examined to determine whether a correlation exists between the nature of goblet cell mucin and the number of crypts (crypt multiplicity) comprising the ACF. According to the ACF score calculated from the results of the qualitative observation of sulfomucins (SuMs) and sialomucins (SiMs), the ACF in the 4th week showed a weak correlation between the nature of the mucus and crypt multiplicity, and the ACF of each class showed similar mucous profiles. From the 8th week, a significant difference ( P <0.01) was recognized between the ACF consisting of 3 crypts or less and those consisting of 4 crypts or more. The proportion of crypts with SiM predominance showed a decrease in the 8th.week in the ACF consisting of 1 crypt and in the 12th week in the ACF consisting of 2 or 3 crypts, implying a recovery tendency. The ACF consisting of more than 4 crypts showed little change over time, retaining the tendency of SiM predominance. Ulex europaeus agglutinin-I (UEA-I) lectin-positive crypts appeared in the ACF. This finding was significantly more prominent ( P < 0.001) in the ACF with SiM predominance than in the ACF with SuM predominance at each experimental period, and in the 12th week after the first administration of DMH, the incidence of ACF with UEA-I-reactive mucin was decreased in the ACF groups consisting of 3 crypts or less, compared with the ACF groups consisting of 4 or more crypts.These results suggest that the biological quality of mucus in ACF consisting of 4 or more crypts is different from that in ACF consisting of 3 crypts or less. This difference should be considered when ACF are used as an intermediate biomarker of colon cancer.     

Cloacogenic carcinoma of the anal canal and associated viral lesions. An in situ hybridization study for human papilloma virus.

Five cases of cloacogenic carcinoma were analyzed for microscopic human papilloma virus (HPV)-induced changes and with in situ hybridization technique for HPV types 6/11, 16/18 and 31/35/51. Four of the five cases showed epithelial foci of koilocytotic atypia. HPV type 16/18 was present in four of the five cases. The surface epithelium in two of the four cases with koilocytotic changes showed HPV type 16/18. HPV type 6/11 was seen in surface epithelium in one case in which invasive carcinoma showed HPV type 16/18. This double infection with double morphologic expression could mean that the same behavioral pattern (anal intercourse) may contribute to both anal condyloma and carcinoma and, although patients with condyloma are at risk for carcinoma, condyloma may not be the precursor lesion in all cases with coexistent condyloma and carcinoma. Because of the similarity between pathogenesis of anal and cervical carcinomas, a periodic cytologic screening of anal mucosa could be indicated in populations at risk: homosexual men, patients with condyloma, women having dysplasia or carcinoma of the uterine cervix, and patients with immunosuppressive disorders.     

Changes in serum lipids related to the presence of experimental colon cancer

People at risk from coronary heart disease and large bowel cancer are drawn from the same urbanised, industrialised Western populations. Whilst changes in blood lipids are well recognised in heart disease, little is known of their role in large bowel cancer. This study investigates serial alterations in blood lipids in the 1,2-dimethylhydrazine (DMH) rat model of colon cancer. Eighty Wistar rats received a 5 weekly regimen of DMH. At week 10, and at 5 weekly intervals until week 40, random groups of 10 rats were killed and blood taken for total and free cholesterol, phospholipids, triglycerides and liver enzymes. All colonic neoplasms were histologically classified either as adenomas or carcinomas with groups being allocated into tumour-free (n = 16) or tumour-bearing (n = 54), the latter group being further sub-divided into animals with adenoma alone (n = 8) and those with carcinoma (n = 46). Results were considered both sequentially and according to tumour status. Sequential results showed that with increase in colonic neoplasms with time there were accompanying increases in free and % free cholesterol and in phospholipids (P less than 0.001). There were no changes in total cholesterol, triglycerides or liver enzymes. Results according to tumour status showed that whilst there was no difference in total cholesterol or triglycerides between tumour-free and tumour-bearing rats, there was a significant increase in free (P less than 0.01) and % free cholesterol (P less than 0.001) and a decrease in phospholipids in the tumour-bearing animals (P less than 0.001). There was no difference in any serum lipid between tumour-free and adenoma-bearing rats. In animals with carcinoma, while there was no difference in total cholesterol or triglycerides, there was an increase in free (P less than 0.005) and % free cholesterol (P less than 0.001) and a decrease in phospholipids (P less than 0.001) compared to tumour-free rats. The data show for the first time a clear relationship between blood lipids and the presence or absence of large bowel cancer.