This proposal resulted from a collaborative effort between Eaton and Research Core Director Helmut Zarbl, and experiments are already underway to compare patterns of gene expression in response to aflatoxin in yeast and mammalian cells. Aspergillus flavus and Aspergillus parasiticus. Worldwide, aflatoxins are considered a major public health problem because of their potent carcinogenic effects. Human epidemiological data has documented that humans are susceptible to AFB-induced hepatocarcinogenesis, especially in combination with hepatitis B virus infection. However, there are large species differences in the susceptibility to aflatoxin carcinogenesis.
Rats are highly sensitive, whereas mice are very resistant.
Treatment of rats with a drug called oltipraz, or a food additive called ethoxyquin, protects rats from aflatoxin-induced liver cancer. Human liver tissue has very low ability to detoxify aflatoxin, less even than the low ability of rat liver tissues. There has been considerable interest in devising a dietary or chemointervention strategy that increases human resistance to AFB by induction of GSTs. Recent clinical chemointervention trials with oltipraz have suggested that this approach may be successful, although the mechanism of action may be via inhibition of cytochrome P450 mediated activation of AFB, rather than induction of GST-mediated detoxification. The Core also serves as the nucleus for collaborations among CEEH investigators whose research focuses on the genetic variation in sensitivity to carcinogens.