BROMODEOXYURIDINE - A DIAGNOSTIC-TOOL IN BIOLOGY AND MEDICINE .1. HISTORICAL PERSPECTIVES, HISTOCHEMICAL METHODS AND CELL-KINETICS

Bromodeoxyuridine (BrdUrd), a thymidine analogue incorporated into DNA , can be quantified by fluorescent or chromophoric quenching of dyes b ound to DNA or with antibodies to BrdUrd. These technologies have been used since the 1970s as tools for measuring DNA synthesis in isolated chromosomes and in cells and tissues. This paper is Part I of a three -part comprehensive review of the literature over the last 20 years (t o the end of 1993) describing the histochemical methods for measuring BrdUrd in cells and tissues. Fixation, denaturation and staining proce dures are compared for quantifying BrdUrd for microscopy and flow cyto metry. Non-immunochemical methods related to the quenching of fluoresc ent DNA stains by BrdUrd are also described. Methods are described for the comparative assay of cell kinetic parameters by tritiated thymidi ne and bromodeoxyuridine. The multivariate BrdUrd/DNA assay of T-s, an d T-c, and a comparison of recent methods based on the single biopsy b ivariate analysis of T-pot, is presented. Recent developments in the u se of double halopyrimidine label to determine kinetic parameters are also reviewed.