TY - JOUR
T1 - The chemical carcinogen, chloroacetaldehyde, modifies a specific site within the regulatory sequence of human cytomegalovirus major immediate early gene in vivo
AU - Kohwi‐Shigematsu, Terumi
AU - Nelson, Jay A.
PY - 1988
Y1 - 1988
N2 - The reaction of chemical carcinogens with DNA is well documented, but whether this interaction occurs at specific sites in chromatin is unknown. We have examined in vivo the reaction of a known carcinogen, chloroacetaldehyde, with the active and inactive major immediate early gene of human cytomegalovirus. We found that during active transcription of the gene, this chemical carcinogen reacts with a unique DNA site in the 5′ flanking sequence of the major immediate early gene. However, no reaction was detected in infected nonpermissive cells in which the gene was inactive. The chloroacetaldehyde‐reactive site is located at ‐836 pmn 10 bp from the mRNA cap site in the part of the regulatory region that can both negatively and positively affect promoter activity [Nelson et al., Mol Cell Biol 7:4125–4129, 1987]. These results suggest, at least in the case of chloroacetaldehyde, the possibility that the molecular mechanism of chemical carcinogenesis involves a chemical reaction at specific sites in chromatin within the sequences responsible for regulation of gene expression. Such carcinogen‐DNA interaction occurs as a consequence of a non‐B DNA structure that contains unpaired DNA bases existing at specific sites in chromatin.
AB - The reaction of chemical carcinogens with DNA is well documented, but whether this interaction occurs at specific sites in chromatin is unknown. We have examined in vivo the reaction of a known carcinogen, chloroacetaldehyde, with the active and inactive major immediate early gene of human cytomegalovirus. We found that during active transcription of the gene, this chemical carcinogen reacts with a unique DNA site in the 5′ flanking sequence of the major immediate early gene. However, no reaction was detected in infected nonpermissive cells in which the gene was inactive. The chloroacetaldehyde‐reactive site is located at ‐836 pmn 10 bp from the mRNA cap site in the part of the regulatory region that can both negatively and positively affect promoter activity [Nelson et al., Mol Cell Biol 7:4125–4129, 1987]. These results suggest, at least in the case of chloroacetaldehyde, the possibility that the molecular mechanism of chemical carcinogenesis involves a chemical reaction at specific sites in chromatin within the sequences responsible for regulation of gene expression. Such carcinogen‐DNA interaction occurs as a consequence of a non‐B DNA structure that contains unpaired DNA bases existing at specific sites in chromatin.
KW - DNase I‐hypersensitive sites
KW - Key words
KW - Non‐B DNA structure
KW - positive and negative regulatory element
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U2 - 10.1002/mc.2940010107
DO - 10.1002/mc.2940010107
M3 - Article
C2 - 2855599
AN - SCOPUS:0024247168
SN - 0899-1987
VL - 1
SP - 20
EP - 25
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 1
ER -