Chinese hamster ovary cells deficient or proficient in O6-alkylguanine-DNA alkyltransferase activity are equally sensitive to X-rays.
In mammalian cells, under aerobic conditions, ionizing radiations and radiomimetic chemical agents can induce an enzymatic activity involved in DNA repair, O6-alkylguanine-DNA alkyltransferase (O6-AT). This catalytic protein is active against alkyl-radical-induced DNA damages. This induction was proposed to be linked to the formation of hydroxyl radicals. The possible involvement of O6-AT in the defense mechanism of the cell against aerobic radiation damage was investigated by comparing the X-ray sensitivity of two Chinese hamster ovary (CHO) cell lines, the first deficient (CHO mex-) and the second proficient by transfection of O6-AT (CHO mex+). The colony-forming ability after X-irradiation was appreciably reduced in CHO mex- in comparison to CHO mex+ cells. Nevertheless, pretreatment of proficient cells with O6-methylguanine, a specific inhibitor of O6-AT, reduced the DNA repair activity but did not modify the degree of sensitivity to X-rays of the CHO mex+ cells. Since the glutathione concentrations as well as the DNA damage amounts induced by X-irradiation were comparable in the variously treated cell lines, these results suggest that the observed induction of O6-AT by ionizing radiation in aerobic conditions could be a generalized rather than a specific response to damage by radicals.
Pardini
C
C
Genetica e Biochemica Tossicologica dell'Istituto di Mutagenesi e Differenziamento-CNR, Pisa, Italy.
Piras
A
A
Voliani
M
M
Rainaldi
G
G
Mariani
L
L
Taverna
P
P
D'Incalci
M
M
Citti
L
L
D000478:Alkylation; D000818:Animals; D016466:CHO Cells / Q000201:enzymology / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D016166:Free Radical Scavengers; D005978:Glutathione / Q000032:analysis; D008780:Methyltransferases / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011836:Radiation Tolerance
D016166:Free Radical Scavengers; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005978:Glutathione