Tumour levels of O6-alkylguanine-DNA-alkyltransferase and sensitivity to BCNU of human xenografts.
Tumour levels of O6-alkylguanine-DNA-alkyltransferase (O6 AT) and glutathione content (GSH) were correlated with 1, 3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) sensitivity in two human ovarian cancer xenografts (HOC8 and HOC18) and in two human glioblastoma xenografts (HG12 and HG15). HOC8 and HOC18, which were not responsive to BCNU treatment, showed O6 AT levels 14 and 23-fold higher than HG12 that was moderately sensitive to the same BCNU treatment. HG15, which was more sensitive to BCNU than HG12, showed significantly lower O6 AT levels. GSH levels were similar in all tumor xenografts. These data further stress the importance of O6 AT level as a relevant parameter for nitrosourea response in human tumours.
Tagliabue
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Citti
L
L
Massazza
G
G
Damia
G
G
Giavazzi
R
R
D'Incalci
M
M
D000818:Animals; D002330:Carmustine / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005978:Glutathione; D002330:Carmustine