title: Pharmacokinetic analysis in serum of genistein administered subcutaneously to neonatal mice.
abstract: Genistein, the principal soy isoflavone, was previously shown to induce uterine adenocarcinomas by 18 months of age in female CD-1 mice following administration by subcutaneous injections on postnatal days 1-5. A serum pharmacokinetic analysis of genistein in male and female mice treated identically showed that: maximal concentrations of total (conjugated+aglycone) genistein in females (6.8+/-1.4 microM) and males (3.8+/-1.1 microM, mean+/-SD) were comparable to those previously reported from dietary exposures in adult rats or in human infants consuming soy formulas; the average fraction present as active aglycone (31%) was similar to those in fetal and neonatal rats from placental and lactational exposures; and elimination half-times were longer than those in rats (three- to seven-fold) and adult humans (two- to three-fold). These results are consistent with a diminished capacity for enzymatic conjugation of genistein, based on the ontogeny, as an important determinant of estrogenicity in neonatal mice.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA. ddoerge@nctr.fda.gov
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Twaddle
authors.forename: Elizabeth Padilla
authors.initials: EP
authors.lastname: Banks
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Jefferson
authors.forename: Retha R
authors.initials: RR
authors.lastname: Newbold
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics*; D005260:Female; D019833:Genistein / Q000493:pharmacokinetics*; D006207:Half-Life; D007279:Injections, Subcutaneous; D008297:Male
chemical_list: D016588:Anticarcinogenic Agents; D019833:Genistein