Assessment of Human Exposure to Carcinogens using DNA Damage as Biomarkers

Humans are inevitably exposed to carcinogens from environmental, occupational, medicinal and life-style sources. Current approaches to evaluating carcinogenic risk rely on information that is extrapolated from animal studies. These studies are carried out at high exposure levels, often at maximum tolerable doses, and the dose responses observed extrapolated linearly to low exposure levels. Results from such direct extrapolations are unreliable because of the large differences in dose response observed between rodents and humans and differences in the mechanism of action at low levels of exposure encountered in environmental or occupational settings compared with the high exposures in animal experiments. A better approach is to assess the internal dose of a toxic compound by measuring the extend of chemical interaction of the compounds with biological macromolecules (e.g. nucleic acids and proteins). Such measurements are preferable to those of external doses because they take into account individual differences in genetics, absorption, metabolism, distribution, and excretion. The determination of the dose of active compounds that reaches the target site of action within the body enables one to estimate the risk associated with the exposure. We are interested in developing sensitive techniques for detecting DNA damage and using DNA damage as biomakers for the assessment of human exposure to carcinogens.