Effects of aging on the induction of angiosarcoma

Adult, Sprague-Dawley albino rats of four different ages (6, 18, 32 and 52 weeks) were exposed to 940 ppm vinyl chloride by inhalation for 24 weeks, 5 days/week, 7 hr/day. In each age group, there were 110 to 128 males and the same number of females. The similarly housed control group, which was not exposed to vinyl chloride, consisted of the same number of males and females in each age group. All animals that died spontaneously, or were sacrificed moribund, or were killed at scheduled times (3, 6 and 9 months after initial exposure) were autopsied. All organs were examined grossly, and several tissues from each animal were examined microscopically. The older the rats were when they were first exposed, the greater the incidence of angiosarcomas. The incidences of angiosarcomas in the four age groups (from youngest to oldest) in the exposed males in the nonscheduled sacrifice groups were: 0/37 (0%); 0/44 (0%); 3/45 (6.7%); and 13/55 (24%). Similarly, for the females, these incidences were: 2/38 (5.3%); 7/47 (15%); 23/49 (47%); and 11/54 (20%). Most of the angiosarcomas were highly anaplastic, primary tumors in the livers that metastasized to the lungs. Only one angiosarcoma was seen in all the control rats; that occurred in subcutaneous tissue. This study demonstrated that older adult animals and females are more susceptible to the angiosarcoma-inducing effects of vinyl chloride than young adult animals and males, respectively.