Protective effects of glucose-6-phosphate and NADP against alpha-chaconine-induced developmental toxicity in Xenopus embryos.
In previous studies a metabolic activation system (MAS) composed of Aroclor 1254-induced rat liver microsomes led to an apparent reduction of potato glycoalkaloid developmental toxicity in the frog embryo teratogenesis assay-Xenopus (FETAX). The reasons for this reduction were investigated in this study. The effect of the exogenous MAS on glycoalkaloid developmental toxicity was examined in two experiments in which a concentration series of alpha-chaconine was tested with a MAS with and without a reduced nicotinamide adenine dinucleotide (NADPH) generator system consisting of NADPH, oxidized nicotinamide adenine dinucleotide (NADP), glucose-6-phosphate (G6P) and glucose-6-phosphate dehydrogenase. The NADPH generator system and each of its individual components were tested at a single high concentration of alpha-chaconine to evaluate their potential effects on toxicity. The findings indicated that the protective effect of the MAS was not the result of detoxification by microsomal enzyme systems, but was caused by two components of the NADPH generator system, namely NADP and G6P. G6P was more protective of alpha-chaconine-induced toxicity than NADP at the concentrations tested. Thus, FETAX with a MAS must be performed with appropriate controls that take into account the possible interactions with individual components of the system.
Rayburn
J R
JR
US Environmental Protection Agency, Environmental Research Laboratory, Gulf Breeze, FL 32561, USA.
Bantle
J A
JA
Qualls
C W
CW
Friedman
M
M
D000818:Animals; D001711:Biotransformation; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D047108:Embryonic Development; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012992:Solanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests; D014981:Xenopus / Q000196:embryology
D005958:Glucosephosphates; D013723:Teratogens; D012992:Solanine; C011860:alpha-chaconine; D009249:NADP; D019298:Glucose-6-Phosphate