Department of Biochemistry, Covenant University, Ota 112233, Ogun State, Nigeria.
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Int J Environ Res Public Health. 2021 Jan 12;18(2):589. doi: 10.3390/ijerph18020589.
Aflatoxins are toxic compounds produced by molds of the species that contaminate food primarily in tropical countries. The most toxic aflatoxin, aflatoxin B1 (AFB1), is a major cause of hepatocellular carcinoma (HCC) in these countries. In sub-Saharan Africa, aflatoxin contamination is common, and perinatal AFB1 exposure has been linked to the early onset of HCC. Epigenetic programming, including changes to DNA methylation, is one mechanism by which early life exposures can lead to adult disease. This study aims to elucidate whether perinatal AFB1 exposure alters markers of offspring health including weight, lipid, and hormone profiles as well as epigenetic regulation that may later influence cancer risk. Pregnant rats were exposed to two doses of AFB1 (low 0.5 and high 5 mg/kg) before conception, throughout pregnancy, and while weaning and compared to an unexposed group. Offspring from each group were followed to 3 weeks or 3 months of age, and their blood and liver samples were collected. Body weights and lipids were assessed at 3 weeks and 3 months while reproductive, gonadotropic, and thyroid hormones were assessed at 3 months. Prenatal AFB1 (high dose) exposure resulted in significant 16.3%, 31.6%, and 7.5% decreases in weight of the offspring at birth, 3 weeks, and 3 months, respectively. Both doses of exposure altered lipid and hormone profiles. Pyrosequencing was used to quantify percent DNA methylation at tumor suppressor gene and growth-regulator in DNA from liver and blood. Results were compared between the control and AFB1 exposure groups in 3-week liver samples and 3-week and 3-month blood samples. Relative to controls, DNA methylation in both low- and high-dose exposed rats was significantly decreased in liver samples and increased in the blood ( < 0.05 in linear mixed models). methylation was higher in the liver from low- and high-exposed rats and decreased in 3-month blood samples from the high exposure group ( < 0.05). Further research is warranted to determine whether such hormone, lipid, and epigenetic alterations from AFB1 exposure early in life play a role in the development of early-onset HCC.
黄曲霉毒素是由种类的霉菌产生的有毒化合物，主要污染热带国家的食物。毒性最强的黄曲霉毒素，黄曲霉毒素 B1（AFB1），是这些国家肝细胞癌（HCC）的主要原因。在撒哈拉以南非洲，黄曲霉毒素污染很常见，围产期 AFB1 暴露与 HCC 的早期发病有关。表观遗传编程，包括 DNA 甲基化的变化，是早期生活暴露导致成人疾病的一种机制。本研究旨在阐明围产期 AFB1 暴露是否改变后代健康的标志物，包括体重、脂质和激素谱，以及可能影响癌症风险的表观遗传调节。受孕前、整个孕期和哺乳期，将怀孕的大鼠暴露于两种剂量的 AFB1（低剂量 0.5 和高剂量 5mg/kg），并与未暴露组进行比较。每组后代分别在 3 周或 3 个月时进行随访，并采集其血液和肝脏样本。在 3 周和 3 个月时评估体重和脂质，在 3 个月时评估生殖、促性腺激素和甲状腺激素。产前 AFB1（高剂量）暴露导致后代出生时、3 周和 3 个月时体重分别显著下降 16.3%、31.6%和 7.5%。两种剂量的暴露都改变了脂质和激素谱。焦磷酸测序用于定量肿瘤抑制基因 和生长调节剂 中 DNA 的 DNA 甲基化百分比。在 3 周龄肝脏样本和 3 周和 3 个月龄血液样本中，将控制组和 AFB1 暴露组的结果进行比较。与对照组相比，低剂量和高剂量暴露组的大鼠肝脏中 DNA 甲基化均显著降低，而血液中则增加（线性混合模型中 < 0.05）。低剂量和高剂量暴露大鼠肝脏中的 甲基化水平较高，高剂量暴露组 3 个月血液样本中的 甲基化水平降低（<0.05）。需要进一步研究，以确定生命早期 AFB1 暴露引起的此类激素、脂质和表观遗传改变是否在早发性 HCC 的发展中起作用。
