THE FORMATION AND REMOVAL OF CISPLATIN (CDDP) INDUCED DNA ADDUCTS IN A CDDP SENSITIVE AND RESISTANT HUMAN SMALL CELL LUNG-CARCINOMA (HSCLC) CELL-LINE

被引:18
作者
HOSPERS, GAP [1 ]
DEVRIES, EGE [1 ]
MULDER, NH [1 ]
机构
[1] STATE UNIV GRONINGEN HOSP,DEPT INTERNAL MED,OOSTERSINGEL 59,9713 EZ GRONINGEN,NETHERLANDS
关键词
D O I
10.1038/bjc.1990.18
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In DNA digested samples of a CDDP sensitive (GLC4) and an 11-fold resistant (GLC4-CDDP) hSCLC line, the CDDP induced DNA adducts Pt-GG (Pt-(NH3)2d (pGpG)), Pt-AG (Pt-(NH3)2d (pApG)), G-Pt-G (Pt-(NH3)2d (GMP)2) and Pt-GMP (Pt-(NH3)3d GMP), were measured with polyclonal antibodies. The total amount of platinum (Pt) bound to DNA was also measured but with the help of atomic absorption spectroscopy (AAS). An increased net formation in GLC4 compared with GLQ-CDDP is found for the total Pt bound to DNA, Pt-GG and Pt-AG adducts after a 2 h IOOjim CDDP treatment. No significant difference is detected in the net formation of the Pt-GMP and G-Pt-G adducts. A slow Pt-AG adduct formation, with a maximum reached 10 h after CDDP composition, is found for both cell lines. In the 22 h period after the 2 h100 JIM CDDP treatment, a significant removal in GLC4 is measured for the Pt-GG, Pt-AG and the Pt-GMP adducts. For GLC4-CDDP a significant removal is detected in the total Pt bound to DNA, the Pt-AG and the Pt-GMP adducts. The removal of the total Pt bound to DNA in GLC4-CDDP cannot be explained by an adduct measured with the immunochemical method. In conclusion, no evidence is found that CDDP resistance is based upon the repair of the Pt-GG, Pt-AG, G-Pt-G and Pt-GMP adducts. © Macmillan Press Ltd., 1990.
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页码:79 / 82
页数:4
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