Sister chromatid induction by beta-irradiation from incorporated 3H-thymidine: a paradox explained.

Abstract

Sister chromatid exchanges (SCE's) induced by [3H]thymidine (3HdT) of increasing specific activities incorporated over one cycle and 5-bromodeoxyuridine (BrdUrd) over the two following cycles were investigated in synchronised Chinese hamster ovary (CHO) cells. SCEs induced during the first cycle on a T.T template (SCE 1) show little increase with dose compared with those induced in the second cycle on a 3HT.T template (SCE 2) where the linear increase with dose reflects that seen after X irradiation. During the third cycle, SCEs 3.1 and 3.2 are induced on unlabelled T.B or labelled 3HT.B templates respectively. These templates are theoretically present in a 1:1 ratio after random segregation at second metaphase. Over practically the entire dose range however, the ratio 3.1/3.2, which decreased with dose, was greater than 1.0 and similar to the high values obtained by other workers. At increasing times after BrdUrd introduction, the ratio decreased from greater than 1.0 to less than 1.0. Measurements showed that the expected 50% level of labelled chromosomes at metaphase in the samples could vary between 42%-59%. Cells with greater than 50% labelled chromosomes were more delayed in the cell cycle due to the 3H-irradiation than those with less than 50%. Early fixations therefore favoured SCE 3.1 while late favoured SCE 3.2. SCEs due to BrdUrd in 3HT.B and T.B templates showed no synergistic interaction with irradiation-induced SCEs. When these BrdUrd-induced SCEs were removed from the totals then the 3H-induced SCE levels in 3HT.T, and 3HT.B templates (SCE 2 and 3.2) were similar and increased at a similar rate with dose. This was 2-3 times faster than in SCE 1 and 3.1 where the SCE levels due to irradiation were again similar but lower than for 2 and 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)