THE DEVELOPMENT OF SEXUAL DIMORPHISM IN NATURAL-KILLER-CELL ACTIVITY AND RESISTANCE TO TUMOR-METASTASIS IN THE FISCHER-344 RAT

The development of sexual dimorphism in the number and activity level of natural killer (NK) cells was studied in the inbred Fischer 344 rat from prepubescence to maturity. Additionally, in view of the biologic al significance of NK cells in controlling cancer, especially the meta static process, we used a syngeneic mammary tumor (MADB106) to assess the host anti-metastatic activity. This tumor model was used because N K cells control the lung clearance of i.v.-injected MADB106 tumor cell s, a process that critically affects the metastatic colonization of th ese tumor cells in the lungs. The results indicated that although prep ubescent (36 days of age) males and females exhibited equivalent numbe rs of large granular lymphocyte (LGL)/NK cells (mAb 3.2.3-positive) pe r mi blood, females exhibited greater NK cytotoxicity (assessed in vit ro) and higher anti-metastatic activity, evidenced by fewer tumor cell s retained in the lungs. On the other hand, the mature males (140-170 days of age) displayed greater LGL/NK number and activity per mi blood , retained fewer tumor cells, and developed fewer lung tumor colonies compared to the females. During early postpubescence (63 days of age), a transitional stage between prepubescence and maturity, females and males exhibited equivalent numbers of circulating LGL/NK cells, and fe males displayed slightly greater NK cytotoxicity per mi blood yet reta ined somewhat greater numbers of tumor cells compared to the males. Ov erall, whereas the males exhibited increasing levels of NK number and activity throughout the age span tested, the females, despite displayi ng greater NK function compared to the males at prepubescence and slig ht improvement at postpubescence, fell behind the males in these indic es of NK function at maturity.