Biomedical subjects
Publications and source records attributed to M A Georgsson.
The question of whether cellular radiation sensitivity is independent or related to plating efficiency (PE) is addressed. Three different cell lines, one human and mortal (AG 1522), one rodent and immortal (CHO AA8), and one rodent and mortal (C3H 10T1/2), were investigated. The first two showed a strong correlation between radiation sensitivity and PE, even when, for the mortal cells, the effect of passage number was factored out.
The effects of cellular GSH levels on the cytotoxicity of MNNG and mitomycin C were examined in normal and BSO treated mouse C3H10T1/2 cells. MNNG was less cytotoxic in the GSH depleted cells (less than 10% of normal) whereas the cytotoxicity of mitomycin C was not influenced by thiol status. This is compatible with the alkylating agent MNNG requiring thiols for activation to the methylating electrophile. Conversely, thiols have little if any effect in modulating the activity of mitomycin C. When naturally thiol deficient human fibroblasts were compared with BSO treated fibroblasts depleted to a similar GSH level (less than 10% of normal), only the BSO depleted cells were less effected by MNNG. The GSH deficient cells showed the same MNNG dose response as normal human fibroblasts. These studies indicate that a naturally acquired thiol status and an equivalent induced thiol status need not behave the same and this needs consideration when evaluating the role of thiols in influencing cellular response to chemotherapeutic agents.
The dipyridilium compound, paraquat, has been used in conjunction with mouse C3H 10T1/2 cells to determine if this superoxide (O2-) generating agent acts to oncogenically transform, chromosomally alter or influence cytokinetics or cellular survival. Paraquat alone is a cytotoxic agent and is additionally a weak radiosensitizer. A 0.1 mM 24 hour treatment results in about 30% cell survival and enhances the cell killing effects of 137Cs gamma rays by a factor of about 1.2. The drug appears to function lethally by initiating an interphase cell death, and additionally slows the movement of cycling cells through the cell cycle. It is a poor inducer of SCE's and combined effects with radiation are strictly additive. Paraquat oncogenically transforms cells but not in a dose-dependent manner, yet combined treatments with 3 Gy result in transformation frequencies greater than expected for additive effects. Depending on the endpoint examined, which may be related to the degree of nuclear involvement, paraquat either acts additively (SCE's) or with greater than an additive effect (cell survival and oncogenic transformation).