Detection of adducts arising from human exposure to N-nitroso compounds.
Humans are exposed to carcinogenic nitroso compounds (NOC), which are likely to result in the formation of DNA adducts. DNA adducts can be detected in human samples using a range of different analytical methodologies, including high pressure liquid chromatography (HPLC)-fluorescence, immunoassays and gas chromatography-mass spectrometry. Immunohistochemical studies offer the possibility of detecting adducts in single cells, but require further development for human studies. Sensitive 32P-postlabelling methods, in conjunction with HPLC separation, allow the detection of NOC-derived alkylated nucleotides in small samples of DNA derived from human tissues such as lymphocytes and placenta. In many studies, adducts have been detected in human DNA, but are often present, to a similar extent, in control and exposed subjects. In a number of studies, exposure to NOC has been inferred from the presence of characteristic alkyl adducts. In subjects from high risk areas for oesophageal cancer, DNA from target tissue contained higher levels of 0(6)-methyldeoxyguanosine than controls. The analysis of adducts in 'surrogate' DNA from peripheral lymphocytes appears promising as an accessible measure of alkylation damage. Also, the measurement of excreted levels of alkylpurines has the potential to be a noninvasive indication of short-term exposure to NOC. Endogenous synthesis of NOC can occur by a number of possible pathways in humans, and measurements of adducts will be a means of detecting the resulting alkylating agents, since their direct detection would be extremely difficult.
Shuker
D E
DE
International Agency for Research on Cancer, Lyon, France.
D000478:Alkylation; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D004781:Environmental Exposure; D007158:Immunologic Techniques; D007553:Isotope Labeling; D009603:Nitroso Compounds / Q000032:analysis / Q000378:metabolism*; D013057:Spectrum Analysis
D009603:Nitroso Compounds; D004247:DNA