TY - JOUR

T1 - Increased paracellular permeability of tumor-adjacent areas in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats

AU - Bekusova, Viktoria V

AU - Falchuk, Evgeny L

AU - Okorokova, Larisa S

AU - Kruglova, Natalia M

AU - Nozdrachev, Alexander D

AU - Markov, Alexander G

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Objective: The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending colon. Inflammatory bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine (DMH)-induced colon adenocarcinoma.Methods: The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical microscopy.Results: Rats with DMH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however, the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier function.Conclusions: The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their barrier function.

AB - Objective: The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending colon. Inflammatory bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine (DMH)-induced colon adenocarcinoma.Methods: The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical microscopy.Results: Rats with DMH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however, the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier function.Conclusions: The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their barrier function.

KW - крыса, 1,2-диметилгидразин, рак толстой кишки, камера Уссинга, ток короткого замыкания, трансэпителиальное сопротивление, проницаемость

KW - Rat; 1,2-dimethylhydrazine; colorectal cancer; Ussing chamber; short circuit current; transepithelial electrical resistance; intestinal permeability

KW - Rat

KW - Short circuit current

KW - Colorectal cancer

KW - Intestinal permeability

KW - Ussing chamber

KW - Transepithelial electrical resistance

KW - 1,2-dimethylhydrazine

UR - http://www.scopus.com/inward/record.url?scp=85055428944&partnerID=8YFLogxK

U2 - 10.20892/j.issn.2095-3941.2018.0016

DO - 10.20892/j.issn.2095-3941.2018.0016

M3 - Article

C2 - 30197792

VL - 15

SP - 251

EP - 259

JO - Cancer Biology and Medicine

JF - Cancer Biology and Medicine

SN - 2095-3941

IS - 3

ER -