title: Effects of the genotoxic agent 5-bromo-2'-deoxyuridine with or without pre-pubertal gonadectomy on brain monoamines and their metabolites in female rats.
abstract: A nucleotide analog 5-bromo-2'-deoxyuridine (BrdU) is a genotoxic compound. Previous studies have demonstrated that prenatal treatment of rodents with BrdU affects the development of cortical neurons, reduces dopamine levels, and elevates serotonin (5-HT) levels in the striatum in adult male offspring from BrdU-treated dams. Moreover, prenatal BrdU-treated rats show locomotor hyperactivity in both males and females. This study investigated sexual dimorphism in the effect of prenatal BrdU on monoamine metabolism. Sprague-Dawley rats were treated with BrdU on gestational days 9-15 (50mg/kg, i.p.) and monoamine metabolism was examined in female rats at 10 weeks of age. The influence of pre-pubertal gonadectomy on the effects of BrdU was also investigated. BrdU-treated females showed elevations of dopamine and 5-HT levels in the striatum; reductions in dopamine, dihydroxyphenylacetic acid, or homovanillic acid (HVA) in the hypothalamus or the midbrain; and elevated HVA and 5-HT in the hippocampus. Pre-pubertal gonadectomy had a suppressive effect on striatal dopamine levels in prenatal BrdU-treated females. The present data indicate sexual dimorphic effects of prenatal BrdU-treatment in striatal dopamine metabolism but not in serotonergic metabolism and suggest a contribution of the increasing gonadal hormones that accompany puberty to this sex difference.
authors.affiliation: Hatano Research Institute, Food and Drug Safety Center, Kanagawa 257-8523, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kuwagata
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D001972:Bromodeoxycytidine / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D005260:Female; D008297:Male; D010052:Ovariectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015306:Biogenic Monoamines; D001972:Bromodeoxycytidine; D001973:Bromodeoxyuridine