thymidine analog reduces life span

From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Thu Dec 23 1999 - 13:23:23 MST


Authors
  Anisimov VN. Osipova GYu.
Institution
  Laboratory of Experimental Tumors, N.N. Petrov Research Institute of
  Oncology, St. Petersburg, Russia.
Title
  Life span reduction and
  carcinogenesis in the progeny of rats exposed neonatally to
  5-bromo-2'-deoxyuridine.
Source
  Mutation Research. 295(3):113-23, 1993 Aug.
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 estrus 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 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.



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