Relationship between DNA-adduct formation, DNA repair, mutation frequency and mutation spectra

DNA-adduct formation by a series of ethylating agents was determined and correlated with induction of gene mutations. This approach gave information concerning the DNA-adduct(s) likely to be responsible for the observed mutations. A methodology has been developed which is used for the DNA sequence analysis of point mutations in the HPRT gene of mammalian cells. This method can be used to obtain mutation spectra and to determine whether the base-pair changes do occur at those sites where DNA-adducts are likely to occur. Measurements of DNA repair in specific DNA sequences show that actively transcribed genes are repaired faster than the genome overall. This stresses the importance of studying removal DNA-adducts in the gene that is used for the analysis of mutation induction.