What is the significance of increases in background levels of carcinogen-derived protein and DNA adducts? Some considerations for incremental risk assessment.
Mutat Res
; 424(1-2): 275-86, 1999 Mar 08.
Article
en En
| MEDLINE
| ID: mdl-10064867
Improvements in analytical methodology have led to the detection and quantification of 'background' levels of a number of DNA and protein adducts. Many of these adducts are derived from 'low molecular weight' reactive species which may be generated during normal physiological processes, metabolic pathways or inflammatory processes. The adducts have been detected using gas chromatography-mass spectrometry, HPLC in combination with various detection systems, 32P-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 hydroxyl radical damage. The accurate and specific quantitation of 'background' levels of damage is essential if reliable estimates of increases in risk associated with incremental increases in exposure to exogenous agents are to be calculated. In experimental studies using low dose exposures to carcinogens, such as N-nitrosodimethylamine, adduct levels in liver correlate closely with tumour incidence. In all likelihood, such relationships need to be established for each exposure and, in order to be relevant to human risk assessment, need to take into account factors such as DNA repair and mutagenic efficiency. Finally, in order to estimate the increase in cancer attributable to a given level of external exposure, it is clearly important to establish background levels of corresponding DNA damage so that the scale of the incremental increase can be calculated.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinógenos
/
Proteínas
/
Mutagénesis
/
Aductos de ADN
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mutat Res
Año:
1999
Tipo del documento:
Article
Pais de publicación:
Países Bajos