Cancer induction is presently considered to be the main risk to human beings from exposure to low doses of ionizing radiation. Effective human radiogenic cancer risk estimation will be based on understanding the cellular and molecular events leading from the initial ionizing event through its expression as a neoplasm. Such an understanding must be based not only on the action of radiation alone but on its interactions with environmental carcinogens, promotors, initiators, inhibitors, and other modifying agents. We have shown that repeated low-level x-radiation enhances carcinogenesis by 7,12-dimethylbenz(a)anthracene (DMBA) in hamster epithelium in vivo. We have suggested, as a likely mechanism, that radiation induces increases in covalent binding of DMBA to DNA. We propose to study the effects of acute and split low to moderate x-radiation exposures on the adduct formation between DMBA and cheek pouch epithelial DNA both in vivo and in organ culture. DNA will be extracted and purified by homogenization-phenol-ethanol procedures. DMBA binding to DNA will be measured by scintillation spectrometry. Control pouches and pouch cultures will be exposed to single or repeated applications of 3H-DMBA. Experimental pouches and pouch cultures will receive 3H-DMBA plus acute or split radiation exposures from 5 - 500R. Radiation exposures will be either prior to, during, or following 3H-DMBA treatments. DMBA-DNA adduct formation and removal will be studied as functions of time, DMBA concentration, radiation dose, split vs. acute radiation exposure, and relative timing of DMBA and radiation treatment.
| Lurie, A G; Coghill, J E; Rozenski, D L (1988) 7,12-Dimethylbenz[a]anthracene adduct formation with Syrian hamster cheek pouch epithelial DNA: in vitro studies in organ explant culture. J Natl Cancer Inst 80:407-14 |
| Lurie, A G; Rozenski, D L; Coghill, J E (1988) DNA adduct formation by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium in vivo. Cancer Res 48:2025-8 |
