The Role of Cereal Mycotoxins as Human Carcinogens

摘要

Most countries have introduced legislation to control the levels of aflatoxins in food but it is not known if these permitted levels still pose a significant cancer risk. It is unlikely that all the sources of human aflatoxin exposure have been discovered, nor if the liver is the only, or indeed major target organ for aflatoxin-induced cancer in man. We have used both immunological and HPLC methods to examine human DNA from a variety of tissues and organs to identify and quantify aflatoxin-DNA adducts. We have already detected Aflatoxin B1 (AFB1) DNA adducts in formalin-fixed tissue from an acute poisoning incident in Southeast Asia. Here we have examined human colon and rectum DNA from normal and tumorous tissue obtained from cancer patients and colon. liver, pancreas, breast and cervix DNA from autopsy specimens. AFB1-DNA adducts were detected in all tissue types examined and ranged from 0-60 adducts /10~6 nucleotides. Where sample size allowed the adduct levels were confirmed by HPLC analysis. Tumor tissues tended to have higher adduct levels than normal tissue from the same individual, and levels generally increased with patient age. In samples analyzed by HPLC the adducts present had the chromztographic properties of (8,9 -dihydro-8-(N~5-formyl) 2', 5', 6'-triamino-4'-oxo-(N~5 - pyramidyl) -9-hydroxi-aflatoxin B1), the ring-opened form of the AFB1-guanine adduct. The level of adducts observed in individuals from the UK where often in the same range as those seen in citizens of Third-World countries. AFB1-DNA adduct values in this range, i.e., 1/10~6, have been reported to result in the development of tumors in rats and trouts dosed with AFB1. This world indicate that aflatoxins may pose a carcinogenic risk to a variety of organs and that there are either unknown sources of aflatoxin in our that the present permitted level in food is too high.