J Korean Cancer Assoc.  2000 Dec;32(6):1075-1083.

N-nitrosomorpholine Directed Preneoplastic Reprogramming of Nuclear Metabolism of Rat Hepatocytes

• Kim MC
• Jeong JS
• Choi YC
• Jung GJ
• Kim SS

Abstract

PURPOSE: An attempt was made to investigate N-nitrosomorpholine (NNM) induced carcinogenic processes in rat liver.
MATERIALS AND METHODS
Rats were fed with NNM (200 mg/l) for 7 weeks, after then stopped. Length of telomere and activity of telomerase were analyzed. Hepatocytes were isolated and grown on tissue culture. Heat shock was treated at 43oC, and patterns of cell death ere evaluted by fluorescent study. Nuclei and nucleoli were isolated for analysis of various signal molecules.
RESULTS
Shortening of telomere length presented in NNM treated liver, but induction of telomerase was not found. Ex vivo hepatocytes from 10~12th week showed increased heat shock resistance at 43oC. NNM-treated hepatocytes exhibited heat shock induced cell death (necrosis) after 7 hours, whereas the control showed necrosis after 3 hours. The signal molecules related to nucleolar growth revealed increased expression which included B23, C23, p38, Erk1/2 and p120. Partial degradation of B23 and Erk2 was noted in necrosis of NNM treated hepatocytes induced by heat shock.
CONCLUSION
The hepatocytes at the stage of 10~12th week in the stop experiment of NNM are situated in the tumour promotion. Those cells showed various metabolic alterations. We found that the increased growth related signals were accompanied with increased heat shock resistance, telomere shortening but no induction of telomerase.

Keyword

N-nitrosomorpholine; Preneoplastic reprogram; Nucleolar signals; Heat shock resistance

MeSH Terms

Animals
Cell Death
Hepatocytes*
Hot Temperature
Liver
Metabolism*
Necrosis
Rats*
Shock
Telomerase
Telomere
Telomere Shortening
Telomerase