Effects Of Chronic Emotional Stress On The Occurrence Of Liver Tumor Of C3H/HeJ Male Mice

OBJECTIVES: To study the effects of chronic emotional stress on the liver tumor occurrence of C3H/HeJ male mice, explore the role of Ha-ras,serum corticosterone, natural killer cell activity and interleukin-2 in the mechanism of tumor occurrence.METHODS: 56 six-month-old C3H/HeJ male mice were divided into chronic emotional stressed(CES) group which was exposed to drinking-conflict stress and restraint stress and non-treated control(C) group. Mice were decapitated in batches at the end of 0(N=16) 2 (N=20)or 4(N=20) months after being grouped, then we removed mice liver and prepared histology section and stained with H&E, counted the morbidity of liver tumor; determined expression of Ha-ras mRNA in the liver of C3H/HeJ male mice by RT-PCR, determined the plasma corticosterone, natural killer cell activity in spleen and the production of interleukin-2 of from splenocyte .RESULTS: (1) In months 2 and 4, accumulative liver tumor morbidity of CES group was significantly higher than that of C groups (P=0.004); In CES group, tumor morbidity of 2-month and 4-month mice significantly increased compared to 0-month mice (P=0.035 and P=0.004) (2) Expression of Ha-ras mRNA of mice with tumor burden is significantly higher than that of mice without tumor burden(P=0.031); In CES group ,the level of Ha-ras mRNA of 4-month mice is significantly higher than that of 2-month mice (P=0.020). (3) In months 2, plasma corticosterone level was elevated in CES group than C group (P=0.016);In months 4, the plama corticosterone level of CES group declined, but was never lower than basal level of month 0. (4) In months 2 and 4, NK cell activity of CES group is significantly lower than that of C group (P=0.046 and P=0.003). (5) In months 2, the production of IL-2 of CES group is significantly lower than that of C group (P=0.001); IninCES group, the level of IL-2 of 2-month and 4-month mice is significantly lower than that of 0-month mice (P=0.018 and P=0.048).(6) Analyzed by logistic regression, the odds ratio (OR)of liver tumor is 1.684(P=0.099) average month and 12.881 (P=0.001) for stressed to unstressed.CONCLUSIONS: Chronic emotional stress can(l) promote the onset of liver tumor of mice, which character is elevation of morbidity and early occurance of liver tumor.(2) influence the expression of Ha-ras mRNA and mediate the occurrence of liver tumor. (3) influence the endocrine and immune system, including plasma corticosterone, activity of NK cell and level of IL-2, mediate the occurrence of liver tumor.(4) On the whole, psychological stress probably mediate the occurrence of liver tumor through multi-system and various level of organ, cell, protein and gene.