Inhibitors of thymidylate synthetase, 5-fluoro-2'-deoxyuridine (FUDR) and 5fluorouracil (FU) , enhanced in uitm thymidine labeling of human breast carcinoma cells. Their use resulted in an increase in the measured thymidine labeling index (TLI) of breast carcinomas by increasing detectability of labeled nuclei in autoradiographs. The TLI was measured with FU or FUDR enhancement in primary breast carcinomas from nine women younger than age 50, and from 30 women 50 years or older. The mean and geometric mean TLI were 8.0 and 6.3 respectively for the younger group, and 4 .O and 2.8 respectively for the older group. Similar significant age-associated differences were noted in a series of 133 TLI measurements without FU or FUDR. The TLI was not significantly correlated with primary breast carcinoma size or number of axillary nodal metastases. The capacity to form axillary metastases must be related to factors other than the rate of cell replication in breast carcinomas.
Cancer 39 : 25 24 -2532, 1 9 77.
HE THYMIDINE LABELING INDEX (TLI) OF A
T population of cells is a measure of the proportion of cells that are synthesizing DNA at the time of exposure to tritiated thymidine (3H-TdR) or other radiothymidine.I7 Cells that have incorporated TI-TdR into deoxyribonucleic acid (DNA) are detected by autoradiography.
The amount of *H-TdR incorporated into a nucleus that is synthesizing DNA (S-phase) during the interval of exposure to 3H-TdR must be sufficient to allow unequivocal detection in autoradiographs, or the TLI will not accurately represent the proportion of cells in the DNAsynthesizing phase of the replicative cycle. If the great majority of nuclei labeled after exposure to W-TdR is heavily labeled, the observer may be confident that few S-phase cells have escaped