Radiosensitization by bromodeoxyuridine and hyperthermia: analysis of linear and quadratic parameters of radiation survival curves of two human tumor cell lines

J Radiat Res. 2001 Jun;42(2):179-90. doi: 10.1269/jrr.42.179.

Abstract

Sensitization by bromodeoxyuridine (BrdUrd) and hyperthermia (HT) on cell reproductive death induced by ionizing radiation was analyzed using the linear-quadratic [S(D)/S(0)=exp(-(alphaD + betaD2)]] model. Plateau-phase human lung tumor cells (SW-1573) and human colorectal carcinonoma cells (RKO) were treated with BrdUrd, radiation and HT. LQ-analysis was performed at iso-incubation dose and at iso-incorporation level of BrdUrd. and at iso-HT doses and iso-survival levels after HT. Clonogenic assays were performed 24 h after treatment to allow repair of potentially lethal damage (PLD). In SW cells BrdUrd. HT or the combination significantly increased the alpha-parameter (factor 2.0-5.7), without altering the beta-parameter. In RKO cells sensitization with BrdUrd increased both a (factor 1.4) and beta (factor 1.3) while HT only influenced beta (factor 2.1-4.0). The combination did not further increase the a and beta. The results indicate that BrdUrd has its main effect on the parameter alpha, dominant at clinically relevant radiation doses but that HT can affect both a and beta. The addition of BrdUrd and HT provides a method to enhance the efficacy of radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bromodeoxyuridine / pharmacology*
  • Cell Death
  • Hot Temperature*
  • Humans
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / physiology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Radiation-Sensitizing Agents
  • Bromodeoxyuridine