P-postlabelling: a Sensitive Technique for the Detection of Dna Adducts

Organisms including humans are exposed to many chemical carcinogens by both endogeneous and exogeneous sources. Of over 600 different agents evaluated for their overall carcinogenicity by the International Agency for Research on Cancer (IARC), more than fifty háve been considered to be carcinogenic in humans. Most of the chemical carcinogens are known to be activated to reactive intermediates that bind to nucleophilic centers in proteins and nucleic acids thereby forming covalent adducts'. The formation of DNA adducts is regarded as a critical early step in the multistage process of carcinogenesis. Moreover, approximately 90 % of the chemicals considered as carcinogenic for humans form DNA adducts. Although the majority of such DNA damage (DNA adducts) is eliminated by DNA repair processes, some persistent adducts often cause permanent mutations in important growth-controlling genes or loci, resulting in aberrant cellular growth and cancer". Therefore, DNA adducts represent a detectable and critical step in chemical carcinogenesis, and thus may serve as an early biomarker for cancer. Thus, the detection of the DNA adducts has become extremely important in risk assessment of chemicals as well as in determinations of exposures to carcinogens for humans. For an assay to be applicable in human exposure settings, it must (i) be sensitive enough to detect low levels of adducts; (ji) require only microgram quantities of DNA; (iii) give results quantitatively related to exposure; (ÍV) be applicable to unknown adducts that may be formed from complex mixture and (v) be able to resolve, quantitate and identify adducts.