What is the significance of increases in background levels of carcinogen-derived protein and DNA adducts? Some considerations for incremental risk assessment

Improvements in analytical methodology have led to the detection and quanti fication of 'background' levels of a number of DNA and protein adducts. Man y of these adducts are derived from 'low molecular weight' reactive species which may be generated during normal physiological processes, metabolic pa thways or inflammatory processes. The adducts have been detected using gas chromatography-mass spectrometry, HPLC in combination with various detectio n systems, P-32-postlabelling and immunoassay methods. The reliability and accuracy of many widely used methods for adduct measurements are discussed with reference to several examples where human data is available, namely 4- aminobiphenyl, malondialdehyde, methylating agents, ethylene oxide and hydr oxyl radical damage. The accurate and specific quantitation of 'background' levels of damage is essential if reliable estimates of increases in risk a ssociated with incremental increases in exposure to exogenous agents are to be calculated. In experimental studies using low dose exposures to carcino gens, such as N-nitrosodimethylamine, adduct levels in liver correlate clos ely with tumour incidence. In all likelihood, such relationships need to be established for each exposure and, in order to be relevant to human risk a ssessment, need to take into account factors such as DNA repair and mutagen ic efficiency. Finally, in order to estimate the increase in cancer attribu table to a given level of external exposure, it is clearly important to est ablish background levels of corresponding DNA damage so that the scale of t he incremental increase can be calculated. (C) 1999 Elsevier Science B.V. A ll rights reserved.