GENDER-SPECIFIC GROWTH AND HEPATIC NEOPLASIA IN MEDAKA (ORYZIAS-LATIPES)

Brief exposure of hatchling medaka (Oryzias latipes);. to diethylnitro samine (DEN), resulted in hepatic tumor formation in female medaka at an incidence of 2-3-fold higher than that of their male cohorts. Spont aneous liver tumor incidence was reported in unexposed 3-5 year old me daka. Gender differences were seen; higher incidence was in the female s. Aspects of gender-specific growth in hatchling, immature and sexual ly mature control medaka are reported and studies sought to determine whether growth enhanced tumorigenesis in females. From a pool of 2000 mixed-sex, 3 week old medaka hatchlings, 1350 were exposed to an aqueo us bath of 250 ppm DEN for 48 h. Another 650 hatchlings served as cont rols. For each fish, body-and liver-weights were recorded (BW and LW,, respectively) and LW to BW ratio (hepatosomatic index-HSI) was estima ted. Next, livers and carcasses were processed for histopathology. BWs of control females were significantly greater than that of males at w eeks 8, 20, 32 and 44 (P < 0.05). LWs and HSIs were significantly grea ter in females versus males at all ages (P < 0.05). In the DEW-treated medaka, female BWs were significantly more than their male counterpar ts at weeks 8, 16, 20 and 32 (P < 0.05). Female LWs were greater than male values at all weeks except 4 and 6 (P < 0.05). Female HSIs were s ignificantly greater than male HSIs at all times (P < 0.05). A higher incidence of foci of cellular alteration (40%) distinguished females f rom males (10%) at week 4 and these values reached 100% incidence (fem ales) and 90% (males) al week 12. Tumor latency periods for adenomas a nd carcinomas were significantly shorter in females than in males. At week 20, the incidence of tumors was significantly higher in females t han in males (P < 0.05). Results indicate that gender-specific differe nces appear in BW, but especially LW and HSI as a function of larval d evelopment, ovarian maturation and age in control and DEN-treated meda ka. Tumor incidence and time to endpoint (latency period) demonstrate that female growth is a promotional-stimulus, positively modulating DE N hepatocarcinogenesis. (C) 1998 Elsevier Science B.V. All rights rese rved.