MURINE INTER-SEX DIFFERENCE IN METHYLCHOLANTHRENE INDUCED TUMOR AND ITS CORRELATION WITH NK ACTIVITY

Susceptibility to 3-methylcholanthrene (MC) induced tumor development between adult male and female C3H mice at 3-4 mo. old was examined. Animals that were injected (s.c.) with a tumorigenic dose (150-mu-g/mouse) of MC demonstrated a significant difference in the latent period of tumor development between both sexes. Female mice were more responsive and developed tumors at 3 wks after treatment, whereas, male mice were less responsive as indicated by the longer latent period (10 wks). In order to correlate these data with activity of natural killer (NK) cells, splenic NK activity was measured by 4 hr Cr-51-release assay. The results showed male mice having higher activity: 27 lytic units (LU) in comparison to female ones (3 LU). This was attributed to a decrease in the lytic effect of female NK cells (11%) compared to male mice (20%), since the binding capacity of effector cells to their targets was similar in both sexes (15%), as indicated by single cell assay. The possible role of an immunosuppressive factor (IF) in the sera of female mice was investigated. NK cells from young females demonstrated 33% suppression in activity post culture with sera from 3-4 mo. old female mice. In conclusion, this study demonstrates a sex-linked tumor development by MC treatment, and correlates this phenomenon with differences of NK activity between young male and female mice as well as in the age-dependent decline of reactivity. A possible immunosuppressive mechanism may be operative in explaining as to why MC is more effective in tumorigenesis in female mice as opposed to males.