Replication of acetylaminofluorene-adducted plasmids in human cells: Spectrum of base substitutions and evidence of excision repair

Journal Article · Thu Nov 14 23:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.22.10193· OSTI ID:5603094

Mah, M C; Boldt, J; Maher, V M; McCormick, J J ^[1]; Culp, S J ^[2]

---

1. Michigan State Univ., East Lansing (United States)
2. National Center for Toxicological Research, Jefferson, AR (United States)

In rats fed the liver carcinogen 2-acetylaminofluorene (AAF), the two most abundant types of DNA adduct are N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and its deacetylated derivative. When plasmids carrying AAF adducts replicate in bacteria, the predominant mutations are frameshifts, whereas with deacetylated (AF) adducts, they are mainly base substitutions, just as the authors found when plasmids carrying AF adducts replicated in human cells. The authors have investigated the frequency and spectrum of mutations induced when a shuttle vector carrying AAF adducts (85% bound to the C8 position of guanine, 15% to the N{sup 2} position) replicated in human cells. The frequency induced per initial AAF adduct was higher than with AF adducts, but the kinds of mutations were similar - i.e., 85% base substitutions, principally G {center dot} C {yields} T {center dot} A transversions. There was good correlation between the hot spots for mutations and hot spots for AAF adduct formation, suggesting that mutational hot spots reflect preferential binding of the carcinogen to DNA. {sup 32}P-postlabeling analysis of the adducts before and after the DNA was transfected of AAF adducts and that 85% of both types of adducts were removed within 3.5 hours, most probably by excision repair.

• OSTI ID: 5603094
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:22; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLAMINOFLUORENES
ADDUCTS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOMAS
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DNA ADDUCTS
DNA REPAIR
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
EVEN-ODD NUCLEI
EXCISION REPAIR
GENETIC EFFECTS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MUTATION FREQUENCY
NEOPLASMS
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
RADIOISOTOPES
RATS
RECOVERY
REPAIR
RODENTS
SULFUR 35
SULFUR ISOTOPES
VERTEBRATES