DNA Double-strand Break Induction and Rejoining as Determinants of Human Tumour Cell Radiosensitivity. A Pulsed-field Gel Electrophoresis Study

Author： Whitaker S.J.   Ung Y.C.   McMillan T.J.  

Publisher： Informa Healthcare

ISSN： 1362-3095

Source： International Journal of Radiation Biology, Vol.67, Iss.1, 1995-01, pp. : 7-18

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Measurement of the surviving fraction after 2 Gy (SF2) may predict for local control of the tumour and patients cure, but clonogenic assays are unsuitable for wider clinical application. Promising results have been obtained using DNA damage assays such as pulsed-field gel electrophoresis, PFGE. In the current study, nine human tumour cell lines (SF2, range 0·08-0·62) were studied for DNA double-strand break (dsb) induction and six of these for dsb rejoining using PFGE. Differences in dsb induction, as the slope (±SEM) of DNA release per Gy, varied from 1·30 (0·05) to 2·42 (0·17). The dsb induction frequency varied from 3·55 (0·33) to 9·69 (2·18) dsb × 10−9/bp/Gy (21-56 dsb/Gy/cell). Variations in the half-time for fast phase (18-60 min) and slow phase (38-445 min) dsb rejoining were observed. Statistically significant correlations were found between SF2 and the slope of the DNA release curve (p = 0·003), DNA release after 10 Gy (p = 0·029) and 20 Gy (p = 0·011) and slow phase dsb rejoining (p = 0·012). While the underlying mechanisms of cell killing remain unclear, PFGE measurement of dsb induction and rejoining shows great potential as a predictive assay for intrinsic cellular radiosensitivity.

Related content

Oxygen Effect for DNA Double-strand Break Induction Determined by Pulsed-field Gel Electrophoresis

By Whitaker S.J.   McMillan T.J.  

International Journal of Radiation Biology, Vol. 61, Iss. 1, 1992-01 ,pp. : 29-41 (13)

Informa Healthcare

Access to resources Recommend Favorite

DNA Double-strand Break Induction in Yeast by X-rays and α-particles Measured by Pulsed-field Gel Electrophoresis

By Löbrich M.   Ikpeme S.   Haub P.   Weber K.-J.   Kiefer J.  

International Journal of Radiation Biology, Vol. 64, Iss. 5, 1993-11 ,pp. : 539-546 (8)

Informa Healthcare

Access to resources Recommend Favorite

A Comparison of Methods for Calculating DNA Double-strand Break Induction Frequency in Mammalian Cells by Pulsed-field Gel Electrophoresis

By de Almodóvar J.M. Ruiz   Steel G.G.   Whitaker S.J.   McMillan T.J.  

International Journal of Radiation Biology, Vol. 65, Iss. 6, 1994-06 ,pp. : 641-649 (9)

Informa Healthcare

Access to resources Recommend Favorite

Use of Pulsed-field Gel Electrophoresis to Investigate Factors Influencing the Measurement of DNA Double-strand Breaks in Human Brain Tumour Specimens

By Wang J.   Delgado D.A.   Deen D.F.  

International Journal of Radiation Biology, Vol. 67, Iss. 2, 1995-02 ,pp. : 153-160 (8)

Informa Healthcare

Access to resources Recommend Favorite

The Relationship of DNA Double-strand Break Induction to Radiosensitivity in Human Tumour Cell Lines

By McMillan T.J.   Cassoni A.M.   Edwards S.   Holmes A.   Peacock J.H.  

International Journal of Radiation Biology, Vol. 58, Iss. 3, 1990-09 ,pp. : 427-438 (12)

Informa Healthcare

Access to resources Recommend Favorite