Failure of tripeptide colon mitosis inhibitor to suppress the cell proliferation of dimethylhydrazine-induced colonic cancers in rats.
The effects of tripeptide colon mitosis inhibitor (CMI, pGlu-His-Gly-OH) on the proliferation of tumoral cells of dimethylhydrazine (DMH)-induced colonic cancers in rats were studied. Additionally, the effects of CMI on hyperplastic colonic crypts in DMH-treated rats and on normal colonic crypts in carcinogen-untreated rats were estimated. As an index of the cell proliferation the incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used. It was found that the tripeptide significantly suppressed the proliferation of the colonic crypts in normal, carcinogen-untreated rats. However, it failed to suppress the cell proliferation of DMH-induced colonic adenocarcinomas or adenomas and produced only a slight, statistically insignificant decrease of the BrDU labelling index in hyperplastic colonic mucosa of DMH-treated rats. These findings suggest that the process of carcinogenesis might 'switch off' the local negative control of the colonic cell proliferation exerted by endogenous CMI.
Pawlikowski
M
M
Institute of Endocrinology, Medical University of Lódź, Poland.
Zerek-Mełeń
G
G
Stepień
H
H
Lachowicz
A
A
Winczyk
K
K
Szadowska
A
A
D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D000236:Adenoma / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D004127:Dimethylhydrazines; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004127:Dimethylhydrazines; D006131:Growth Inhibitors; D009842:Oligopeptides; C023866:pyroglutamyl-histidyl-glycine; D011761:Pyrrolidonecarboxylic Acid