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High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes
We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long‐Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age‐matched F344 rats were administered an intraperitoneal inje...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1993
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919285/ https://www.ncbi.nlm.nih.gov/pubmed/8407564 http://dx.doi.org/10.1111/j.1349-7006.1993.tb00186.x |
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author | Sakamoto, Hirofumi Sawada, Norimasa Kamimura, Yasuhiro Enomoto, Katsuhiko Mori, Michio |
author_facet | Sakamoto, Hirofumi Sawada, Norimasa Kamimura, Yasuhiro Enomoto, Katsuhiko Mori, Michio |
author_sort | Sakamoto, Hirofumi |
collection | PubMed |
description | We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long‐Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age‐matched F344 rats were administered an intraperitoneal injection of a low dose of DEN. Eight weeks after the injection, the numbers of glutathione‐S‐transferase placental‐form (GST‐P)‐positive foci in the 33‐week‐old LEC rat liver were significantly higher than those in the livers of the other three groups of rats. (2) Potential for unscheduled DNA synthesis (UDS): Isolated hepatocytes of 25‐week‐old LEC rats with chronic hepatitis showed about one‐third the level of UDS induced by UV irradiation, as compared to that of age‐matched F344 rats, while no significant difference was found between the UDS of isolated hepatocytes of 8‐week‐old LEC rats and age‐matched F344 rats. (3) Potential for proliferation: Isolated hepatocytes from 8‐week‐old LEC rats responded well to epidermal growth factor (EGF) in culture, to almost the same degree as F344 rat hepatocytes, while a remarkable decrease in the responsiveness of hepatocytes isolated from 25‐week‐old LEC rats to EGF was found. These results suggested that LEC rat hepatocellular carcinoma could be naturally initiated after the onset of hepatitis by carcinogens contaminating food and the environment, probably due to the reduction of DNA repair activity, after which initiated hepatocytes selectively proliferate in response to growth stimuli endogenously produced as a result of continuous loss of hepatocytes (chronic hepatitis), because of a decrease in growth activity of non‐initiated hepatocytes. |
format | Online Article Text |
id | pubmed-5919285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1993 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59192852018-05-11 High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes Sakamoto, Hirofumi Sawada, Norimasa Kamimura, Yasuhiro Enomoto, Katsuhiko Mori, Michio Jpn J Cancer Res Article We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long‐Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age‐matched F344 rats were administered an intraperitoneal injection of a low dose of DEN. Eight weeks after the injection, the numbers of glutathione‐S‐transferase placental‐form (GST‐P)‐positive foci in the 33‐week‐old LEC rat liver were significantly higher than those in the livers of the other three groups of rats. (2) Potential for unscheduled DNA synthesis (UDS): Isolated hepatocytes of 25‐week‐old LEC rats with chronic hepatitis showed about one‐third the level of UDS induced by UV irradiation, as compared to that of age‐matched F344 rats, while no significant difference was found between the UDS of isolated hepatocytes of 8‐week‐old LEC rats and age‐matched F344 rats. (3) Potential for proliferation: Isolated hepatocytes from 8‐week‐old LEC rats responded well to epidermal growth factor (EGF) in culture, to almost the same degree as F344 rat hepatocytes, while a remarkable decrease in the responsiveness of hepatocytes isolated from 25‐week‐old LEC rats to EGF was found. These results suggested that LEC rat hepatocellular carcinoma could be naturally initiated after the onset of hepatitis by carcinogens contaminating food and the environment, probably due to the reduction of DNA repair activity, after which initiated hepatocytes selectively proliferate in response to growth stimuli endogenously produced as a result of continuous loss of hepatocytes (chronic hepatitis), because of a decrease in growth activity of non‐initiated hepatocytes. Blackwell Publishing Ltd 1993-09 /pmc/articles/PMC5919285/ /pubmed/8407564 http://dx.doi.org/10.1111/j.1349-7006.1993.tb00186.x Text en |
spellingShingle | Article Sakamoto, Hirofumi Sawada, Norimasa Kamimura, Yasuhiro Enomoto, Katsuhiko Mori, Michio High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title | High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title_full | High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title_fullStr | High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title_full_unstemmed | High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title_short | High Sensitivity of LEC Rats with Chronic Hepatitis to Hepatocarcinogenesis: Decreases in Unscheduled and Replicative DNA Synthesis of the Hepatocytes |
title_sort | high sensitivity of lec rats with chronic hepatitis to hepatocarcinogenesis: decreases in unscheduled and replicative dna synthesis of the hepatocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919285/ https://www.ncbi.nlm.nih.gov/pubmed/8407564 http://dx.doi.org/10.1111/j.1349-7006.1993.tb00186.x |
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