Persistence of 5-bromo-2'-deoxyuridine in tissues of rats after exposure in early life.

Outbred L10 rats received 4 subcutaneous injections of 3.2 mg per rat 5-bromo-2'-deoxyuridine (BrdUrd) at 1, 3, 7 and 21 days of age. Groups of rats were sacrificed 1 h, 1 month or 49 weeks after the final injection. Tissues were fixed in 70% ethanol, embedded in paraffin and unstained sections were prepared for immunohistochemical demonstration of BrdUrd. A monoclonal antibody to BrdUrd was used with the avidin biotin peroxidase-complex (ABC) technique. The numbers of immunoreactive nuclei were tissue, cell and time-related. The labeling indices declined from 1 day to 49 weeks for all tissues studied. At 49 weeks after the last exposure to BrdUrd, many cells were still reactive, especially in tissues with normal low cell turnover (brain, uterine stroma). For cells with high turnover, including lymphocytes and ovarian germinative epithelium, few or no labeled cells remained at 49 weeks. This study provides clear evidence for the persistence of BrdUrd in normal tissues, some of which may be targets for the carcinogenic effect of the chemical and others which are not targets.