PMID- 7509623
OWN - NLM
STAT- MEDLINE
DCOM- 19940407
LR  - 20211109
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 8
IP  - 3
DP  - 1993 Nov
TI  - Carcinogen-induced amplification of SV40 DNA inserted at 9q12-21.1 associated 
      with chromosome breakage, deletions, and translocations in human uroepithelial 
      cell transformation in vitro.
PG  - 155-66
AB  - The fate of integrated SV40 viral genome in SV40-immortalized human uroepithelial 
      cells (SV-HUC) during multistep chemical transformation in vitro was studied. We 
      previously reported that exposure of SV-HUC at passage (P) 15 to the chemical 
      carcinogens 3-methylcholanthrene (MCA), 4-aminobiphenyl (ABP), or the N-hydroxy 
      metabolites of ABP causes tumorigenic transformation and/or neoplastic 
      progression. We report now that these same chemical carcinogens induce 
      amplification of SV40 DNA in SV-HUC. We used fluorescence in situ hybridization 
      (FISH) to show that this amplification occurs at the SV40 integration site, which 
      was mapped near a common fragile site at 9q12-21.1 on the der(9)t(8;9) chromosome 
      that is present in all SV-HUC at the earliest passage studied. Karyotypic 
      analysis, along with FISH, also revealed that all carcinogen-induced tumors 
      (T-SV-HUCs) had breaks at 9q12-21.1, deletions of 9q12-21.1-->pter, and new 
      derivative chromosomes containing SV40 in the segment 
      9q12-21.1-->9q34::8q22-->8qter. Southern blot analysis, along with FISH, 
      confirmed SV40 genome rearrangements in T-SV-HUCs. In contrast, no 9q12-21.1 
      breaks were observed in control SV-HUC. Thus, these results associate 
      9q12-21.1-->pter alterations with HUC tumorigenic transformation. In addition, 
      these results indicate for the first time that (carcinogen-induced) amplification 
      of chromosome-integrated viral genes may create sites that are prone to breakage, 
      deletions, and translocations. These results suggest a new mechanism by which 
      chemical carcinogens in synergy with a DNA tumor virus could initiate a cascade 
      of events that contribute to the genomic instability associated with 
      tumorigenesis.
FAU - Kao, C
AU  - Kao C
AD  - University of Wisconsin Comprehensive Clinical Cancer Center, Department of Human 
      Oncology, Madison 53792.
FAU - Wu, S Q
AU  - Wu SQ
FAU - DeVries, S
AU  - DeVries S
FAU - Reznikoff, W S
AU  - Reznikoff WS
FAU - Waldman, F M
AU  - Waldman FM
FAU - Reznikoff, C A
AU  - Reznikoff CA
LA  - eng
GR  - NCI RO1-CA29525/CA/NCI NIH HHS/United States
GR  - P01-CA519871/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Carcinogens)
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Carcinogens/*pharmacology
MH  - Cell Line, Transformed
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - *Chromosome Aberrations
MH  - Chromosome Deletion
MH  - Chromosome Mapping
MH  - Chromosomes, Human, 6-12 and X
MH  - *Chromosomes, Human, Pair 9
MH  - DNA, Viral/analysis
MH  - Gene Amplification/*drug effects
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gene Rearrangement
MH  - Genes, Viral/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Molecular Probe Techniques
MH  - Simian virus 40/drug effects/*genetics
MH  - Translocation, Genetic
MH  - Tumor Cells, Cultured
MH  - Virus Integration
EDAT- 1993/11/01 00:00
MHDA- 1993/11/01 00:01
CRDT- 1993/11/01 00:00
PHST- 1993/11/01 00:00 [pubmed]
PHST- 1993/11/01 00:01 [medline]
PHST- 1993/11/01 00:00 [entrez]
AID - 10.1002/gcc.2870080304 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 1993 Nov;8(3):155-66. doi: 10.1002/gcc.2870080304.