Molecular dosimetry of the chemical mutagen ethyl methanesulfonate: quantitative comparison of mutation induction in Escherichia coli, V79 Chinese hamster cells and L5178Y mouse lymphoma cells, and some cytological results in vitro and in vivo
Aaron, C.S.; van Zeeland, A.A.; Mohn, G.R.; Natarajan, A.T.; Knaap, A.G.; Tates, A.D.; Glickman, B.W.
Mutation Research 69(2): 201-216
1980
ISSN/ISBN: 0027-5107 PMID: 6987499 Document Number: 159935
Molecular dosimetry studies were carried out to measure the extent of binding of radiolabeled ethyl groups to the DNA of E. coli, Chinese hamster V79 lung cells and L5178Y mouse lymphoma cells treated with ethyl methanesulfonate (EMS). The amount of ethylation of the DNA is similar in these cells when treatment conditions are identical, the relationship between dose to DNA (ethylations per nucleotide) vs. exposure (mM applied concentration) is non-linear in the sense that less alkylation of the DNA is observed at higher exposures than would be predicted on the basis of proportionality between dose to DNA and exposure and the non-linearity of the genetic response in the bacterial cells is not reflected in a non-linearity of the alkylation of the DNA in those cells. Quantitative comparision of the frequencies of gene mutations in the various systems shows that the mutation frequency per unit of DNA alkylation is heterogeneous among the mammalian cell systems and that the frequencies observed in the bacterial cells fall within the range observed with mammalian cells. Alkylation of the DNA in the bone marrow, testis and liver of Swiss random-bred mice was also measured. The distribution of the compound to the various tissues is rapid and probably uniform. Quantitative assessment of the cytological data (including micronuclei and sister chromatid exchanges) on the basis of dose was not as useful because of the low efficiency of EMS for inducing cytologically observable damage.