PMID- 9412997
OWN - NLM
STAT- MEDLINE
DCOM- 19980202
LR  - 20220408
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 12
IP  - 6
DP  - 1997 Nov
TI  - Chromosomes with high gene density are preferentially repaired in human cells.
PG  - 437-42
AB  - It is known that DNA repair is heterogeneous in human cells since open chromatin, 
      active genes and their transcribed strands are preferentially repaired. It is 
      thus expected that DNA repair is clustered in chromosomes with high gene density. 
      We have employed a DNA repair inhibitor, cytosine arabinoside (Ara-C), to convert 
      ethyl methane sulfonate (EMS)-induced excision repairable lesions to chromosomal 
      breaks, to check for the existence of heterogeneity of repair at the chromosome 
      level. Chromosome staining by fluorescence in situ hybridization (FISH) was used 
      to analyze breakage in chromosomes with diverse gene densities. These chromosomes 
      were identified by means of the CpG island distribution after FISH with a CpG 
      island-rich probe isolated from total human genomic DNA. Thus, three chromosomes 
      with very high gene density (numbers 1, 19 and 20) were compared with two 
      chromosomes with very low gene density (numbers 4 and 18) for clastogenicity and 
      sensitivity to co-treatment with Ara-C and EMS. Our data indicate that those 
      chromosome with higher gene density are more sensitive to a combination treatment 
      with Ara-C and EMS, indicating that the level of excision repair synthesis is 
      higher in those chromosome. It is therefore concluded that DNA excision repair is 
      preferentially directed to chromosomes with high gene density. The implications 
      of this finding in human biomonitoring using FISH techniques are discussed.
FAU - Surralles, J
AU  - Surralles J
AD  - Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The 
      Netherlands. ibgb6@blues.uab.es
FAU - Sebastian, S
AU  - Sebastian S
FAU - Natarajan, A T
AU  - Natarajan AT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Mutagens)
RN  - 04079A1RDZ (Cytarabine)
RN  - 9H154DI0UP (Ethyl Methanesulfonate)
SB  - IM
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Cells, Cultured
MH  - Chromosome Breakage/genetics
MH  - Chromosomes/*drug effects
MH  - Chromosomes, Human, Pair 1/drug effects
MH  - Chromosomes, Human, Pair 18/drug effects
MH  - Chromosomes, Human, Pair 19/drug effects
MH  - Chromosomes, Human, Pair 20/drug effects
MH  - Chromosomes, Human, Pair 4/drug effects
MH  - CpG Islands/drug effects/genetics
MH  - Cytarabine/pharmacology
MH  - DNA Repair/*drug effects
MH  - Ethyl Methanesulfonate/pharmacology/toxicity
MH  - Genes/drug effects
MH  - Genome, Human
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mutagenesis/drug effects
MH  - Mutagenicity Tests
MH  - Mutagens/*pharmacology/toxicity
EDAT- 1997/12/31 00:00
MHDA- 1997/12/31 00:01
CRDT- 1997/12/31 00:00
PHST- 1997/12/31 00:00 [pubmed]
PHST- 1997/12/31 00:01 [medline]
PHST- 1997/12/31 00:00 [entrez]
AID - 10.1093/mutage/12.6.437 [doi]
PST - ppublish
SO  - Mutagenesis. 1997 Nov;12(6):437-42. doi: 10.1093/mutage/12.6.437.