Distribution of carbon-14 labeled C60 ([14C]C60) in the pregnant and in the lactating dam and the effect of C60 exposure on the biochemical profile of urine.
This study was conducted to determine the distribution of [(14)C]C60 in the pregnant rat and fetuses, and in the lactating rat and offspring. Pregnant rats were dosed on gestation day (gd) 15 and lactating rats were dosed on postnatal day (pnd) 8 via tail vein injection with a suspension of approximately 0.3 mg [(14)C]C60 kg(-1) body weight prepared in polyvinylpyrrolidone (PVP), or with PVP alone. Tissues were collected at 24 and 48 h after dosing. The largest portion of the administered dose was detected in the liver (approximately 43%, pregnant dam; approximately 35%, lactating dam) and lung (approximately 25%, lactating dam). Radioactivity (approximately 6%) was distributed to the reproductive tract, placenta and fetuses of the pregnant dam. Lactating rats had radioactivity distributed to the milk (3140 dpm g(-1) tissue, 24 h; 1620 dpm g(-1) tissue, 48 h), and to the pups' GI tract (2.8%, 24 h; 4.4% 48 h) and liver (<1%). Blood radioactivity was significant at 24 h (14-19%) and at 48 h (7%) after dosing; largely accounted for in the plasma fraction. Less that 4% of the dose was recovered in the maternal spleen, heart, brain, urine or feces. Metabolomics analysis of urine indicated that dams exposed to [(14)C]C60 had decreased metabolites derived from the Krebs cycle and increased metabolites derived from the urea cycle or glycolysis, as well as alterations in the levels of some sulfur-containing amino acids and purine/pyrimidine metabolites. This study demonstrated that [(14)C]C60 crosses the placenta and is transmitted to offspring via the dam's milk and subsequently systemically absorbed.
Sumner
Susan C J
SC
Biomarkers and Systems Biology, Discovery Sciences, RTI International, Research Triangle Park, NC 27709, USA. ssumner@rti.org
Fennell
Timothy R
TR
Snyder
Rodney W
RW
Taylor
George F
GF
Lewin
Anita H
AH
D000818:Animals; D000831:Animals, Newborn; D002250:Carbon Radioisotopes; D005260:Female; D037741:Fullerenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D007774:Lactation; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D055432:Metabolomics; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry*
D002250:Carbon Radioisotopes; D037741:Fullerenes; C069837:fullerene C60