Life span reduction and carcinogenesis in the progeny of rats exposed neonatally to 5-bromo-2′-deoxyuridine

Abstract

Outbred LIO rats were given subcutaneous injections (3.2 mg) of a synthetic analogue of thymidine, 5-bromo-2′-deoxyuridine (BrdUrd) on days 1, 3, 7 and 21 postnatally. At 3 months, the treated males and females were mated to generate F₁ progeny. The mean life span decreased by 31.6% and 9.1% in male rats and by 21.1% and 7.2% in female rats exposed to BrdUrd and in their offspring, respectively. Exposure to BrdUrd increased the aging rate of the rats and of their progeny. Age-related changes in the length of the estruc cycle and in the incidence of persistent estrus and/or anestrus were observed earlier in female rats exposed neonatally to BrdUrd and in their offspring compared to controls; also, developmental stigmas were observed in the offspring of rats exposed neonatally. The incidence of total and malignant tumors was increased in rats that had received BrdUrd as well as in their progeny. Our observations on the decrease in mean and maximum life span, the increase in aging rate, the acceleration of age-related changes in female reproductive system function, and the increase in tumor incidence and decrease in tumor latency in rats exposed to BrdUrd in early life suggest that this system could serve as a model of accelerated aging. These effects persist at least to the next generation.