[Effects of 4-(4"-(2",2",6",6"-tetramethyl-1"-pipe-ridinyloxy) amino)-4'-demethylepipodophyllotoxin on nucleic acids, proteins, and DNA strand of L7712 cells in vitro].
The antitumor activity of GP-7, a new spin-labeled epipodophyllotoxin, was studied by liquid scintillation spectrometry. There were many similarities between GP-7 and etoposide. Both GP-7 and etoposide inhibited the incorporation of [3H]TdR, [3H]UR, and [3H]Leu into DNA, RNA, and protein synthesis in leukemia 7712 cells. The inhibition correlated with drug concentration and duration. IC50 of GP-7 and etoposide on DNA synthesis at 24 h were 0.21 and 0.37 micrograms.ml-1, respectively. The inhibition of GP-7 or etoposide on DNA synthesis retained even after the drug were washed out for 3 h. GP-7 and etoposide caused DNA single-strand breaks, with a well concentration-response relationship. These data suggest that the inhibition of DNA synthesis by GP-7 or etoposide is likely due to the damage of DNA template and breaking of single-strand DNA.
He
X Q
XQ
Department of Pharmacology, Lanzhou Medical College, China.
Zhang
P Y
PY
Tian
X
X
Li
J X
JX
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005047:Etoposide / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; C071346:GP 7; D005047:Etoposide; D011034:Podophyllotoxin