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Titolo:
PARTIAL ATTENUATION OF HYDROXYUREA-INDUCED EMBRYOTOXICITY BY DEOXYRIBONUCLEOTIDES IN MOUSE AND RAT EMBRYOS TREATED IN-VITRO
Autore:
HANSEN DK; GRAFTON TF; CROSS DR; JAMES SJ;
Indirizzi:
US FDA,NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL JEFFERSON AR 72079 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL JEFFERSON AR 72079
Titolo Testata:
Toxicology in vitro
fascicolo: 1, volume: 9, anno: 1995,
pagine: 11 - 19
SICI:
0887-2333(1995)9:1<11:PAOHEB>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-LYMPHOMA CELLS; DNA-SYNTHESIS; RIBONUCLEOTIDE REDUCTASE; TRIPHOSPHATE POOLS; MAMMALIAN EMBRYOS; ORGANOGENESIS; INVITRO; TERATOGENESIS; METABOLISM; PROTECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
D.K. Hansen et al., "PARTIAL ATTENUATION OF HYDROXYUREA-INDUCED EMBRYOTOXICITY BY DEOXYRIBONUCLEOTIDES IN MOUSE AND RAT EMBRYOS TREATED IN-VITRO", Toxicology in vitro, 9(1), 1995, pp. 11-19

Abstract

Hydroxyurea (HU) is a well known developmental toxicant in all animalspecies tested. It inhibits DNA synthesis, and addition of deoxycytidine monophosphate (dCMP) has been shown previously to attenuate the developmental toxicant effects of HU in vivo. The purpose of the presentinvestigation was to determine whether addition of deoxyadenosine monophosphate (dAMP) or dCMP would attenuate HU-induced embryotoxicity using a rodent whole embryo culture system. Rat embryos were removed on the morning of day 10 of gestation, and mouse embryos were removed on day 8 of gestation (day 0 = the day a vaginal plug was found). Embryoswere treated with various concentrations of HU (up to 500 mu g/ml) for 1 hr at 37 degrees C before being washed and cultured for 43 hr in rat serum containing dAMP or dCMP. At the end of the culture period, six endpoints were evaluated for each viable embryo: morphological score; number of somite pairs; crown-rump and head lengths, DNA and proteincontents. HU (300 mu g/ml) significantly decreased values for all endpoints in embryos from both mice and rats; however, mouse embryos appeared to be more sensitive to the effects of the drug. dAMP and dCMP alone produced some embryotoxicity at high concentrations. The combination of HU + dAMP had no consistent beneficial effect in rat embryos andno effect on mouse embryos. The combination of HU + dCMP improved growth and development slightly. As determined by HPLC analysis, HU treatment (300 mu g/ml for 1 hr) decreased all nucleotide pools. Subsequenttreatment with dAMP increased all pool levels, although these levels remained below those of control embryos. These results suggest that the developmental toxicant effects of HU are not due solely to alterations in deoxyribonucleotide pool levels.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 05:44:17