Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats

Sunter, J. P.; Appleton, David R.; Wright, Nicholas A.; Watson, Amanda J.

doi:10.1038/bjc.1978.104

Cited by 20 publications

(9 citation statements)

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“…We have also observed a reduction in growth fraction in the state of hyperplasia which precedes neoploia in the small bowel (Sunter et al, 1978c); in this preneoplastic state no change in T, was evident. It is clear from these observations that documentation of the precise sequence of cytokinetic changes during the neoplastic transformation of the crypt epithelium will lead to a better understanding of the early stages of tumorigenesis.…”

Section: Discussionsupporting

confidence: 52%

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Sunter¹,

Hull²,

Appleton³

et al. 1980

Br J Cancer

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Summary.-We have measured mitotic indices and 3H-thymidine-labelling indices for the colonic epithelial tumours induced in rats by the administration of dimethylhydrazine (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.

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Section: Discussionsupporting

confidence: 52%

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Sunter¹,

Hull²,

Appleton³

et al. 1980

Br J Cancer

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“…This increase in crypt proliferation without change in MI is not unique (Snow & Altmann, 1983; Sunter et al . , 1978). As posited by Snow & Altmann (1983), an increase in crypt cells without change in MI can be explained by either an increase in the number of crypt basal stem cells or an increase in the number of divisions an upper crypt cell (sometimes referred to as a transit-amplifying cell) undergoes prior to differentiation.…”

Section: Application Of the Mode Of Action Frameworkmentioning

confidence: 99%

Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

Thompson

Proctor

Suh

et al. 2013

Critical Reviews in Toxicology

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Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors.

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“…The greatest number of tumors are found in the descending colon, with the ascending colon being the second most common site (Weisburger et al, 1977;Deschner, 1974). The gastric stomach and duodenum, which display borderline repair capabilities for damage resulting from DMH, are infrequent but not unheard of sites for neoplasms, especially in rats (Zedeck and Brown, 1977;Sunter et al, 1978;Celik et al, 1981). The remaining Gl tissues, which demonstrate significant DMH-induced DNA repair capacity, rarely develop tumors (Weisburger et al, 1977;Deschner, 1974;Clapp et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of replicative and repair DNA synthesis in mouse colon following administration of 1,2‐dimethylhydrazine

Koval

1984

Journal of Toxicology and Environmental Health

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Early alterations in normal semiconservative and repair DNA synthesis were determined in gastrointestinal tissues of HalCR mice following administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). Following DMH injections of 60 and 200 mg/kg, normal DNA synthesis was rapidly inhibited in all tissues. The greatest depressions were observed in the descending colon, followed closely by the ascending colon. DNA repair was estimated by measuring unscheduled DNA synthesis. No repair was observable in the descending or ascending colon. The esophagus, forestomach, jejunum, and ileum demonstrated significant amounts of DNA repair, while the duodenum and gastric stomach displayed nominal or insignificant amounts of repair. Repair DNA synthesis was inhibited by simultaneous administration of caffeine and DMH. The degree of inhibition of normal replicative DNA synthesis and the amount of repair DNA synthesis in response to DMH treatment correlate closely with the incidence of DMH-induced tumors. Most tumors occur in the descending colon, followed by the ascending colon, and only a few in the duodenum and gastric stomach area. Neoplasms are rarely found in the remainder of the gastrointestinal system.

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Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats

Cited by 20 publications

References 20 publications

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

Selective inhibition of replicative and repair DNA synthesis in mouse colon following administration of 1,2‐dimethylhydrazine

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