John M. Essigmann, Ph.D., John Groopman, Ph.D.
Massachusetts Institute of Technology, Johns Hopkins University
NIEHS Grants R01ES016313, P01ES006052, P30ES002109, P30ES003819
A new mouse study, funded in part by NIEHS, quantitatively links prenatal DNA damage from the liver carcinogen aflatoxin B1 (AFB1) with risk of cancer later in life. The new results point to the prenatal period as a critical window of susceptibility to genetic damage from toxins that leads to cancer later in life.
AFB1, a toxin produced by fungi that contaminate food supplies, is a potent carcinogen that leads to a type of liver cancer known as hepatocellular carcinoma (HCC) and is especially problematic in the developing world. To quantify the link between AFB1 damage and later development of cancer, the researchers exposed mice embryos to AFB1 and compared the rates of cancer-causing mutations in these mice with adult mice exposed to the same dose.
The data revealed that the DNA adducts produced in the livers of exposed embryos were 20-fold more likely to lead to mutations than the adducts in adults that received the same dose of aflatoxin. These results correlated with Ki67 staining of the liver, which indicated that the fetal liver cells were dividing much faster than adult liver cells.
Based on these findings, the researchers say that it is especially important to prevent maternal exposures to aflatoxins and point to the need to explore preventive measures that improve maternal pathways of metabolism and detoxification to prevent effects from unavoidable exposures to food contaminated with aflatoxins.
Citation: Chawanthayatham S, Thiantanawat A, Egner PA, Groopman JD, Wogan GN, Croy RG, Essigmann JM. 2015. Prenatal exposure of mice to the human liver carcinogen aflatoxin B1 reveals a critical window of susceptibility to genetic change. Int J Cancer 136(6):1254-1262