Superoxide anion production and toxicity in V79 cells of six hydroxy-anthraquinones.
This study investigates the cytotoxic and genotoxic effects of various carboxy AQ, 1,4-dihydroxy 6-carboxy AQ, 1,8-dihydroxy 3-carboxy AQ, 1,4-dihydroxy AQ, 1,5-dihydroxy AQ, 1,8-dihydroxy AQ and 2,6-dihydroxy AQ in V79 Chinese hamster cells. The V79 cells were used since, as they contain flavoproteins but not cytochrome P-450, they can bioactive xenobiotics only through the reductive pathway excluding the oxidative one. In addition, the abilities of AQs to stimulate O2-production using both purified flavoproteins (NADH-dehydrogenase, NADPH-cytochrome P-450 reductase) and V79 subcellular fractions (homogenate and microsomes) were assayed. The NADH and NADPH consumption stimulated by AQs in V79 microsomes was also determined. The results showed that the carboxylic-containing drugs and the 1,4-dihydroxy AQ were weak sister chromatid exchange inducers and the most toxic among the six anthraquinones examined. Dicumarol, a potent inhibitor of DT-diaphorase, reduced, rather than potentiated, both the cytotoxicity and genotoxicity caused by these AQs. Thus, the higher superoxide formation rates stimulated by the carboxylic-containing AQs compared to those of the other quinones with all the in vitro systems used, suggested, except for the 1,4-dihydroxy AQ, a possible relationship between cytotoxicity and O2-production. For the 1,4-dihydroxy AQ toxicity, a specific bioactivation route was hypothesized.
Mian
M
M
Istituto Farmaceutico Gentili Via Mazzini, Pisa, Italy.
Fratta
D
D
Rainaldi
G
G
Simi
S
S
Mariani
T
T
Benetti
D
D
Gervasi
P G
PG
D000818:Animals; D000880:Anthraquinones / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D008861:Microsomes / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D011808:Quinone Reductases / Q000502:physiology; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
D000880:Anthraquinones; D009243:NAD; D013481:Superoxides; D009249:NADP; D009251:NADPH-Ferrihemoprotein Reductase; D011808:Quinone Reductases