Springer Online Journal Archives 1860-2000
Summary The XP cell strain XP29MA, its malignant counterpart XP29MAmal and a normal human fibroblast strain were tested for colony-forming ability after treatment with HECNU in the presence of m6G, m6Gua, and he7G. In XP29MAmal, inhibition of post-HECNU colony-forming ability was 35% when 0.25 mM of either m6G or m6Gua were present, whereas in XP29MA and the normal fibroblast strain no inhibition was detected. The he7G caused a similar but smaller inhibitory effect in XP29MAmal, but failed to do so in XP29MA. HECNU predominantly exerts its killing effect by alkylating O-6 of DNA-bound guanine and causing DNA interstrand crosslinks. Alkylation of O-6 of guanine can be repaired by 6-methylguanine-DNA methyltransferase. From our experiments we conclude that in XP29MAmal this methyltransferase was inhibited in the presence of the 6-alkylguanines, thus leaving more 2-chloroethylated sites in DNA unrepaired. This results in sensitization in terms of decreased colony-forming ability observed only in the malignant cell line.
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