Podophyllin, but not the constituents quercetin or kaempferol, induced genotoxicity in vitro and in vivo through ROS production.
The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.
Lin
Mei Chih
MC
College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Cheng
Hui Wen
HW
Tsai
Yi Chen
YC
Liao
Po Lin
PL
Kang
Jaw Jou
JJ
Cheng
Yu Wen
YW
D000818:Animals; D002869:Chromosome Aberrations / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044949:Kaempferols / Q000302:isolation & purification / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D011033:Podophyllin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011034:Podophyllotoxin / Q000302:isolation & purification / Q000633:toxicity; D011794:Quercetin / Q000302:isolation & purification / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism
D044949:Kaempferols; D009153:Mutagens; D017382:Reactive Oxygen Species; C006552:kaempferol; D011033:Podophyllin; D011794:Quercetin; D011034:Podophyllotoxin