Teratogenic effects of a lipophilic cationic dye rhodamine 123, alone and in combination with 2-deoxyglucose.
An anti-tumor agent, the cationic dye rhodamine 123 (Rh 123), becomes concentrated in mitochondria of certain tissues and inhibits ATP production. Rh 123 was tested for developmental toxicity by i.p. injection into pregnant CD-1 mice daily on gestation days 7-10 (plug = day 1) at doses up to 15 mg/kg/day. Additional mice were given a 500 mg/kg/day dose of 2-deoxy-glucose (2-DOG), an inhibitor of glycolytic ATP generation, alone or with Rh 123. Controls received saline equimolar to the 2-DOG. Prenatal mortality was increased by Rh 123 in combination with 2-DOG, with values of 40%, 43%, or 41% dead or resorbed at Rh 123 doses of 8, 12, or 15 mg/kg/day, respectively. When given alone, neither test agent was associated with a significant increase in prenatal death. Concurrent treatment with Rh 123 and 2-DOG resulted in significant incidences of gross malformations (17% to 20%) and skeletal malformations (9% to 72%). At the two highest Rh 123 doses (12 and 15 mg/kg/day) given with 2-DOG, significant findings included retarded skeletal ossification and variations (up to 83% and 41%, respectively), as well as decreased fetal weight. According to these results, combinations of rhodamine 123 and 2-deoxyglucose administered to the dam during early organogenesis are developmentally toxic to mice.
Hood
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RD
Department of Biology, University of Alabama, Tuscaloosa 35487.
Ranganathan
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Jones
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CL
Ranganathan
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PN
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities; D004396:Coloring Agents / Q000008:administration & dosage / Q000633:toxicity*; D003837:Deoxy Sugars / Q000633:toxicity*; D003847:Deoxyglucose / Q000008:administration & dosage / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D051381:Rats; D020112:Rhodamine 123; D012235:Rhodamines / Q000008:administration & dosage / Q000633:toxicity*; D013723:Teratogens; D014966:Xanthenes / Q000633:toxicity*
D004396:Coloring Agents; D003837:Deoxy Sugars; D012235:Rhodamines; D013723:Teratogens; D014966:Xanthenes; D020112:Rhodamine 123; D003847:Deoxyglucose