Effects of prenatal hydroxyurea-treatment on mouse offspring.
Hydroxyurea (HU), a ribonucleotide reductase inhibitor, induces morphological anomalies in the central nervous system, craniofacial tissues and limb buds in animals, and neonatal respiratory distress in humans. The neonates and offspring of pregnant mice treated with 400 or 800 mg/kg of HU on day 13 of gestation were examined at 0 day and 10 weeks after birth to find a clue for clarifying the relationship between HU-induced apoptosis in the fetal tissues and teratogenicity. The offspring from dams treated with HU were retarded in growth compared with controls. But there was no significant difference in the body weight gain between the 400 and 800mg/kg groups. In the teratologic changes, microencephaly, hydrocephalus and curved coccygeal vertebrae were observed in the offspring, and the incidence of these teratologic changes was similar but their degree was more severe in the 800 mg/kg group than in the 400 mg/kg group. Based on the above-mentioned previous and present studies of ours, we suggest that HU-induced apoptosis in fetal tissues may play an important role in the development of anomalies in the corresponding tissues of offspring.
Woo
Gye Hyeong
GH
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. ghwoo@naver.com
Katayama
Kei-ichi
K
Bak
Eun Jung
EJ
Ueno
Masaki
M
Yamauchi
Hirofumi
H
Uetsuka
Koji
K
Nakayama
Hiroyuki
H
Doi
Kunio
K
D000014:Abnormalities, Drug-Induced; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006918:Hydroxyurea / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy
D006918:Hydroxyurea