Abstract:
: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.
journal_name
Drug Chem Toxicoljournal_title
Drug and chemical toxicologyauthors
Hood RD,Ranganathan S,Jones CL,Ranganathan PNdoi
10.3109/01480548809017882subject
Has Abstractpub_date
1988-01-01 00:00:00pages
261-74issue
3eissn
0148-0545issn
1525-6014journal_volume
11pub_type
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