Abstract 841: Protection of normal tissues by DIM (3,3'-Diindolylmethane) during radiation therapy

Abstract

Abstract 96 Normal 0 false false false EN-US ZH-CN X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-fareast-language:EN-US;} Despite advances in precision targeting of tumors by radiation therapy, local recurrence is still a serious problem due to the inability to sometimes deliver a sufficiently high dose of radiation to achieve tumor control without unacceptable late normal tissue and organ toxicity. DIM (3,3'-diindolylmethane), a commercially available dietary supplement, has long been studied as a cancer prevention and anti-tumor agent. We are investigating DIM's differential effects after radiation in tumor and normal tissues using a mouse model approach. We monitored tumor growth after localized radiation in a tumor engraftment model of MDA-MB-231 human breast carcinoma cells using immunocompromised NSG mice. The fractionated regimen consists of a total dose of 24 Gy in four fractions (6 Gy per fraction given every other day) with administration of DIM or vehicle at one hour prior to each fraction. DIM showed no significant effect on the growth of irradiated tumors, i.e. DIM did not affect the treatment efficacy of radiation on tumors. On the other hand, we are investigating the molecular mechanism of DIM's radio-protective effects in normal tissues. Our transcriptomic data indicate that DIM treatment increases expression of some stress-responsive genes without causing DNA damage. Results to date indicate that DIM might delay radiation-induced cell cycle arrest and apoptosis. The ultimate goal is to develop DIM as a clinical radioprotector in order to improve the therapeutic index by allowing higher doses of radiation to improve local tumor control by reducing late dose-limiting normal tissue toxicity by radiation.<!–EndFragment–> Citation Format: Renxiang Chen, Lijun Li, Loretta Y. Lin, Albert J. Fornace, Heng-Hong Li. Protection of normal tissues by DIM (3,3'-Diindolylmethane) during radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 841.