Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Sunter, J. P.; Hull, Diana; Appleton, David R.; Watson, Amanda J.

doi:10.1038/bjc.1980.207

Cited by 20 publications

(9 citation statements)

References 19 publications

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“…Although meaningful in vivo studies of proliferation rates in these tumours involving repeated sampling and labelling would present obvious ethical problems, the most recent studies on human material in vitro comparing malignant tumours to normal mucosa using stathmokinetic (Pritchett et al, 1982) and 3H-Thymidine labelling (Bleiburg et al, 1976) techniques suggest that cell birth rate and turnover time respectively, were only very slightly increased in tumours or not significantly different. Similar findings have been reported for premalignant polyps in human (Weisburger et al, 1975), and in experimentally induced rodent tumours, where similar proliferation rates for benign and malignant tumours were reported (Sunter et al, 1980). In the tumours, furthermore, the growth fraction is probably actually lower than in the normal mucosa.…”

Section: Resultssupporting

confidence: 87%

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

Spandidos¹,

Kerr²

1984

Br J Cancer

182

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Summary Study of expression of ras-related oncogenes in human premalignant polyps and malignant tumours of the colorectum, as well as in normal colorectal mucosa, shows a significant elevation in the premalignant and malignant tissues as compared to their respective colorectal mucosa. These results suggest that activation of the ras oncogene family occurs in the development of colorectal tumours and that elevated expression at a premalignant stage may well be critical in the process of carcinogenesis but not in itself sufficient.

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Section: Resultssupporting

confidence: 87%

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

Spandidos¹,

Kerr²

1984

Br J Cancer

182

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“…Again, using material from the descending colon, Tutton & Barkla (1976) found that, while crypt length did not alter significantly during DMH treatment, there was a considerable increase in crypt circumference, leading to an increase in cell population from 1300 to 1800 cells. In the present study we have found increases in crypt length and crypt-column count in transverse colon and descending colon, with an increase in population size similar to that observed by Tutton & Barkla (1976 (Sunter et al, 1980). The estimates of growth fraction in the whole crypt show reductions in ascending colon, with no change in the transverse colon.…”

Section: Discussionsupporting

confidence: 91%

“…Transverse blocks of tumours were taken for histology and autoradiography, and the results have been reported elsewrhere (Sunter et al, 1978a;Sunter et al, 1980). In addition to the blocks from the tumours, sections of tumour-free mucosa w,ere obtained from 4 sites:…”

Section: Methodsmentioning

confidence: 99%

“…In the present study we have used the same kinetic techniques to examine the non-neoplastic colonic mucosa of DMHtreated rats, in order to explore the possibility of proliferative changes in such mucosa. The results have been compared with those for a historical control group of normal rats from the same colony and with those for DMH-induced colonic adenocarcinoma (Sunter et al, 1980).…”

mentioning

confidence: 99%

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Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats

Sunter¹,

Watson²,

Appleton³

1981

Br J Cancer

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Summary.-Administration of 1,2 dimethylhydrazine (DMH) to rats by weekly s.c. injections causes the development of multiple epithelial tumours of the large bowel. These appear to arise as localized dysplastic abnormalities in hitherto apparently morphologically normal crypts. This study was undertaken in order to examine cell proliferation in such apparently normal crypts of DMH-treated animals.A number of proliferative abnormalities are evident, including changes in the size of the crypts, changes in the disposition of proliferating cells within them and reduced cell-cycle times. The nature and the extent of the abnormalities vary from site to site along the length of the bowel, and reflect the vulnerability of the different segments of the bowel, not only to the carcinogenic effects of DMH, but also to short-term toxicity.

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“…Carcinomas were further classified into 2 types: tubular adenocarcinomas and nontubular carcinomas. 21,22 The former are well-differentiated gland-forming adenocarcinomas. The latter show abundant mucus production and are further classified into mucinous and signet-ring cell carcinomas.…”

Section: Classification Of Colon Tumorsmentioning

confidence: 99%

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Wei

Morimura

Wanibuchi

et al. 2004

Intl Journal of Cancer

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We have previously demonstrated that JTE-522, a selective cyclooxygenase-2 (COX-2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a putative preneoplastic lesion in colon, and suggested its inhibitory potential in rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE-522, the present study was design to evaluate the inhibitory effects of JTE-522 on rat colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH). Rats at 6 weeks of age were divided into 4 groups. One week after the start of the experiment, all rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week for 4 successive weeks. As the initiation and postinitiation treatment groups, groups 1-3 were fed diets containing 0, 50, or 150 ppm JTE-522, respectively, from the start of the study to the end. As the postinitiation treatment group, group 4 was given 150 ppm JTE-522 from 1 week after the last DMH injection to the end of the study. Forty weeks after the start of the experiment, administration of 150 ppm JTE-522 during both initiation and postinitiation stages significantly inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well as total tumors in the colon. The inhibitory effect of JTE-522 was most prominent for tubular adenocarcinomas, but was not observed in the nontubular carcinomas (signet-ring cell and mucinous carcinomas). Almost equal inhibitory effects on tubular adenocarcinomas were also observed in the rats given 150 ppm JTE-522 during the postinitiation stage, suggesting that its major anticancer action is at the postinitiation phase. However, JTE-522 had no effect on the size or invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses revealed that JTE-522 had no effect on gene expression levels in DMH-induced tubular adenocarcinomas. These findings suggest that JTE-522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon. In view of the significant inhibitory effects of JTE-522 on ACF, its major anticancer action may occur in the postinitiation stage but before the malignant conversion stage of DMH-induced colon carcinogenesis.Key words: JTE-522; selective cyclooxynenase-2 inhibitor; colon carcinogenesis; tubular adenocarcinoma; chemoprevention Colorectal cancer leads to approximately 550,000 annual deaths worldwide 1 and is therefore a major public health problem and underlines the need for effective chemopreventive strategies. The protective effect of traditional nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin and sulindac, for colon cancer has been well documented in epidemiologic and animal studies. 2 However, their use for chemoprevention of colon cancer has been hindered by their potential gastrointestinal and renal toxicity. It is now known that nonselective NSAIDs inhibit activities of cyclooxygenases (COX), and inhibition of COX-2 may well explain their chemopreventive effect, whereas inhibition of COX-1 is believed to be responsible for man...

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Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Cited by 20 publications

References 19 publications

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

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