Implication of Chromosome Structure and Replication on Hazard of Tritiated Thymidine and the Interpretation of Data on Cell Proliferation

Abstract

LABELLING of chromosomal deoxyribonucleic acid (DNA) with tritium-labelled thymidine (H³TDR) demands consideration of the probabilities of long-term retention of the label and damage to somatic and genetic cells. These are important for the interpretation of results and for consideration of hazards associated with the use of tritiated thymidine in human beings. The model proposed by Taylor, Woods and Hughes¹ permits prediction of the persistence of the label, an implication which has not been adequately explored in previous publications by ourselves and others^2–4. The model is based on autoradiographic observations on plant chromosomes labelled with H³TDR during replication. In this model each chromosome is considered to consist of two halves (chromatids), both of which replicate. If H³TDR is available during DNA synthesis for a finite period, both half-chromosomes will be labelled in their newly formed replicas. On division, all chromosomes of the daughter cells will contain the label in the newly replicated chromatid. Subsequent DNA synthesis proceeds without further availability of H³TDR, and newly formed replicas of both labelled and unlabelled chromatids will be unlabelled.