PMID- 6430783
OWN - NLM
STAT- MEDLINE
DCOM- 19840919
LR  - 20220409
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 67
IP  - 2
DP  - 1984
TI  - DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common 
      fragile sites in human chromosomes.
PG  - 136-42
AB  - Aphidicolin, a specific inhibitor of DNA polymerase alpha, is known to induce 
      chromosomal aberrations. At concentrations that did not greatly affect mitotic 
      index, aphidicolin induced a striking number of chromosome gaps and breaks 
      distributed in a highly nonrandom manner in cultured human lymphocytes. Specific 
      chromosome bands, especially 2q31, 3p14, 6q26, 7q32, 16q23, and Xp22 were 
      preferentially damaged in lymphocytes from each of 12 subjects studied. Total and 
      site-specific damage was dose dependent and greatly increased when folic acid was 
      removed from the medium. The sites most sensitive to aphidicolin damage include 
      the "hot spots" seen under conditions of thymidylate stress and in studies of 
      spontaneous chromosomal damage. The fragile X site, which can also be induced by 
      thymidylate stress, was not induced by aphidicolin in lymphocytes, suggesting a 
      separate mechanism for its induction. Aphidicolin represents a novel tool for 
      detection of hot spots on human chromosomes through the mechanism of DNA 
      polymerase alpha inhibition. The hot spots induced by aphidicolin represent a new 
      class of fragile sites which we term common fragile sites.
FAU - Glover, T W
AU  - Glover TW
FAU - Berger, C
AU  - Berger C
FAU - Coyle, J
AU  - Coyle J
FAU - Echo, B
AU  - Echo B
LA  - eng
GR  - CA25055/CA/NCI NIH HHS/United States
GR  - HD 16850/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Culture Media)
RN  - 0 (Diterpenes)
RN  - 38966-21-1 (Aphidicolin)
RN  - EC 2.7.7.7 (DNA Polymerase II)
SB  - IM
MH  - Aphidicolin
MH  - Cells, Cultured
MH  - Chromosome Banding
MH  - Chromosome Fragile Sites
MH  - *Chromosome Fragility
MH  - Chromosomes, Human/drug effects/*ultrastructure
MH  - Culture Media
MH  - DNA Polymerase II/*antagonists & inhibitors/genetics
MH  - Diterpenes/*pharmacology
MH  - Female
MH  - Humans
MH  - Lymphocytes/ultrastructure
MH  - Male
EDAT- 1984/01/01 00:00
MHDA- 1984/01/01 00:01
CRDT- 1984/01/01 00:00
PHST- 1984/01/01 00:00 [pubmed]
PHST- 1984/01/01 00:01 [medline]
PHST- 1984/01/01 00:00 [entrez]
AID - 10.1007/BF00272988 [doi]
PST - ppublish
SO  - Hum Genet. 1984;67(2):136-42. doi: 10.1007/BF00272988.