Leukemia cells, mouse crosslinking

Mouse L1210 leukemia cells DNA fragmentation, DNA-protein crosslink No data + Fornace et al. 1981 Potassium chromate... 

It has been shown that cells can be protected from the toxic effects of cis-PPP by preventing the formation of DNA crosslinks by incubating cells in the presence of thiourea immediately after treatment ( ), a finding which further supports a cytotoxic role for DNA interstrand crosslinks. Further investigation in mouse leukemia cells and human fibroblasts of varying sensitivity to cisplatin, have shown that cellular sensitivity often correlates with interstrand crosslink formation (55, 56, 57). However, studies of certain mouse leukemia L1210 lines resistant to cisplatin (5, ), as well as studies of Walker carcinoma cells (59)... 

Indirect evidence for DNA repair as a determinant in acquired resistance was obtained with the discovery that a mouse leukemia cell line 50-fold resistant to cis-DDP had a fourfold increase in the level of DNA polymerase p, an enzyme involved in DNA repair (73). This hypothesis was supported by a study in which a human ovarian carcinoma cell line 20-fold resistant to cis-DDP showed two to three times more repair synthesis than the parental cell line after a 1-h exposure to the drug (74). Also, studies in L1210 cells found that, although d(GpG), d(ApG), and d(ApNpG) crosslinks formed by [ H][Pt(en)Cl2] were all repaired, resistant cells repaired fourfold more adducts during an initial 6-h phase of repair (39). 

Finally thiourea is found to protect cells against toxic actions produced by platinum complexes including cis-DDP (for instance 62-64). Thus the survival of mouse leukemia L1210 cells treated with cis-DDP was enhanced by posttreatment incubation with thiourea. The mechanism(s) responsible for this protection is believed to involve reversing DNA-cis-DDP crosslinking. It is known that thiourea reacts with platinum-complexes as cis-DDP replacing various ligands from such complexes (65,... 

---