Quantitative comparison of genetic effects of ethylating agents on the basis of DNA adduct formation. Use of O6-ethylguanine as molecular dosimeter for extrapolation from cells in culture to the mouse

Journal Article · Tue Oct 01 04:00:00 EDT 1985 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.2307/3430108· OSTI ID:5632392

van Zeeland, A A; Mohn, G R; Neuhaeuser-Klaus, A E; Ehling, U H

DNA-adduct formation and induction of gene mutations were determined simultaneously after treatment with the four ethylating agents, ethyl methanesulfonate (EMS), ethylnitrosourea (ENU), diethyl sulfate (DES), and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Both, in E. coli K-12 (NAL-resistance) and in V79 Chinese hamster cells in culture (HPRT-deficiency), the frequencies of mutation induction by all chemicals were the same when plotted against the amount of O6-ethylguanine formed in DNA, suggesting that this DNA adduct can be used as a common dosimeter for the comparisons of the frequencies of gene mutations induced by ethylating agents in various mutagenicity assay systems. Using ENU, such a comparison was performed between mutation induction in V79 cells in vitro and in the specific-locus assay in the mouse. The data indicate that at equal levels of O6-ethylguanine in the DNA of V79 cells and in testicular DNA from male mice treated with ENU, the frequencies of induced mutants in both assay systems were quite similar. These results support the concept that the determination of premutagenic DNA adducts in vivo can be used to monitor exposure to chemical mutagens and that genetic risk estimations may ultimately be performed on the basis of such measurements and of comparative mutagenesis in vitro and in vivo.

• Research Organization: State Univ. of Leiden, The Netherlands
• OSTI ID: 5632392
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States); ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
560302 -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BACTERIA
BIOLOGICAL EFFECTS
CHO CELLS
DNA
DNA ADDUCTS
EMS
ENVIRONMENTAL EXPOSURE
ESCHERICHIA COLI
ESTERS
EXTRAPOLATION
GENES
GENETIC EFFECTS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
MAMMALS
MICE
MICROORGANISMS
MUTAGENS
MUTATIONS
NITROSO COMPOUNDS
NITROSOUREAS
NUCLEIC ACIDS
NUMERICAL SOLUTION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
RODENTS
SULFONIC ACID ESTERS
SULFURIC ACID ESTERS
VERTEBRATES