Molecular dosimetry of aflatoxin DNA adducts in humans and experimental rat models.
Primary hepatocellular carcinoma is one of the most common and lethal cancers in the world. It is particularly prevalent on the continents of Africa and Asia. A number of epidemiological studies have associated the exposure status of people to aflatoxin B1 as being important in the etiology of liver cancer. However, to date these studies have relied upon the criteria of presumptive intake data, rather than relying upon quantitative analyses of aflatoxin DNA adduct and metabolite content obtained by monitoring biological fluids from exposed people. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of aflatoxin B1 in people, thereby facilitating risk assessments. In combination with the human monitoring studies is the need to use animals models to help provide an interpretable data base for the human results. Animal models are also going to be critical to the development of chemoprotection strategies. The molecular dosimetry studies described in this chapter support the concept that measurement of the major, rapidly excised AFB-N7-guanine adduct in urine is an appropriate dosimeter for estimating exposure status and possibly risk in individuals consuming this mycotoxin.
Groopman
J D
JD
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205.
Roebuck
B D
BD
Kensler
T W
TW
D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000517:prevention & control; D002681:China; D004247:DNA / Q000378:metabolism*; D004781:Environmental Exposure; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control; D051381:Rats; D013871:Thiones / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use
D000348:Aflatoxins; D000970:Antineoplastic Agents; D013871:Thiones; D013876:Thiophenes; D004247:DNA; C049325:1,2-dithiol-3-thione