Monitoring human exposure to carcinogens by ultrasensitive postlabelling assays: application to unidentified genotoxicants.

The 32P-postlabelling assay is a recently developed analytical tool for the detection and measurement of nucleic acid (DNA and RNA) adducts formed by covalent binding of identified or unidentified electrophiles. The detection limit of the assay for many adducts is as low as 0.3 amol adduct/microgram DNA ( = one adduct/10(10) DNA nucleotides, or one adduct per mammalian genome). As presented here, the method can be applied to DNA alterations elicited by (i) complex mixtures of genotoxicants (e.g., cigarette smoke, occupational exposures), (ii) oestrogens (i.e., hormones that cause DNA damage via the formation of unidentified electrophiles), and (iii) DNA-reactive chemicals that may be formed metabolically in animal tissues without known exposure and give rise to adduct-like DNA alterations (termed I compounds).