Induction of achromosomal cleavage by hydroxyurea in starfish embryo and the reversal by a combination of deoxyadenosine and deoxycytidine: possible involvement of salvage pathway for deoxynucleoside triphosphate biosynthesis in the presence of hydroxyurea.
Effects of hydroxyurea, an inhibitor of ribonucleotide reductase, on cleavage of starfish embryos were studied. In the presence of 1 mM hydroxyurea, fertilized eggs of the starfish, Asterina pectinifera, cleaved up to the 256-cell stage and decomposed before blastulation. Before the 16-cell stage, each blastomere contained a normal nucleus or chromosomes with mitotic apparatus. The cleavage after the 16-cell stage was slow compared to the control embryos, and not all blastomeres contained a nucleus or normal chromosomes. During the fifth cell division (between 16-cell- and 32-cell-stage embryos), chromatin mass unassociated with the mitotic apparatus remained near the cleavage furrow. When hydroxyurea was removed before the 16-cell stage, the embryos developed to normal bipinnalia larvae via normal blastulae. However, the embryos were disintegrated before blastulation when hydroxyurea was removed after the 32-cell stage. DNA synthesis was normally observed before the 16-cell stage but not after the 16-cell stage, but dNTP contents in the embryos remained low throughout development in the presence of hydroxyurea. The achromosomal cleavage observed in the presence of hydroxyurea was reversed by the combination of extracellular dAR and dCR. Therefore, it is assumed that the synthesis of dNTPs required for DNA synthesis in the presence of hydroxyurea occurs via the salvage pathway using deoxynucleosides (dNR) (dNR to dNTP via dNMP and dNDP).
Yamada
H
H
Department of Physiological Chemistry, Tokyo Metropolitan Institute of Medical Science, Japan.
Kuraishi
R
R
Hirai
S
S
Katoh
Y
Y
Fusetani
N
N
Amikura
R
R
Okano
K
K
Nagano
H
H
D000818:Animals; D004261:DNA Replication / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D003841:Deoxycytidine / Q000494:pharmacology*; D003853:Deoxyribonucleosides / Q000096:biosynthesis*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology*; D013215:Starfish
D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D003841:Deoxycytidine; D006918:Hydroxyurea