The vinyl chloride DNA derivative N sup 2 ,3-ethenoguanine produces G yields A transitions in Escherichia coli

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-11, Vol.88:22
• Main Authors: Cheng, K.C., Cahill, D.S., Loeb, L.A., Preston, B.D., Dosanjh, M.K., Singer, B.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; ADDUCTS; ADENINES; AMINES; ANTIMETABOLITES; AROMATICS; AZAARENES; BACTERIA; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL EFFECTS; CHEMICAL REACTIONS; CHLORINATED ALIPHATIC HYDROCARBONS; DAYS LIVING RADIOISOTOPES; DERIVATIZATION; DISEASES; DNA ADDUCTS; DNA BASE TRANSITIONS; DNA POLYMERASES; DNA REPLICATION; DRUGS; ENZYMES; ESCHERICHIA COLI; GUANINE; HALOGENATED ALIPHATIC HYDROCARBONS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; ISOTOPES; LIGHT NUCLEI; MICROORGANISMS; MUTATION FREQUENCY; NEOPLASMS; NUCLEI; NUCLEIC ACID REPLICATION; NUCLEIC ACIDS; NUCLEOTIDYLTRANSFERASES; ODD-ODD NUCLEI; OLIGONUCLEOTIDES; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; PHOSPHORUS-GROUP TRANSFERASES; POLYMERASES; PROTEINS; PURINES; RADIOISOTOPES; SARCOMAS; TRANSFERASES; VINYL CHLORIDE
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.22.9974

Vinyl chloride is a known human and rodent carcinogen that forms several cyclic base derivatives in DNA. The mutagenic potential of these derivatives has been examined in vitro but not in vivo. One of these derivatives, N{sup 2}, 3-ethenoguanine ({var epsilon}G), is known to base pair with both cytosine and thymine during in vitro DNA synthesis, which would result in G {yields} A transitions. To determine the base pairing specificity of this labile guanine derivative in Escherichia coli, the authors have developed a genetic reversion assay for guanine derivatives. The assay utilizes DNA polymerase-mediated analogue insertion into a bacteriophage vector, M13G*1, which detects all single-base substitutions at position 141 of the lacZ{alpha} gene by change in plaque color. They conclude that {var epsilon}G specifically induces G{yields}A transitions during DNA replication in E. coli. The M13G*1 assay may permit the testing of other labile guanine derivatives not otherwise amenable to mutagenesis studies.