Intervention trial with calcium montmorillonite clay in a south Texas population exposed to aflatoxin

South Texas currently has the highest incidence of hepatocellular carcinoma (HCC) in the United States, a disease that disproportionately affects Latino populations in the region. Aflatoxin B(1) (AFB(1)) is a potent liver carcinogen that has been shown to be present in a variety of foods in the U.S., including corn and corn products. Importantly, it is a dietary risk factor contributing to a higher incidence of HCC in populations frequently consuming AFB(1)-contaminated diets. In a randomized double-blind placebo controlled trial, we evaluated the effects of a three-month administration of ACCS100 (refined calcium montmorillonite clay) on serum AFB(1)-lysine adduct level and serum biochemistry in 234 healthy men and women residing in Bexar and Medina Counties, Texas. Participants recruited from 2012–2014 received either a Placebo, 1.5 g, or 3 g ACCS100 each day for three months, and no treatment during the 4(th) month. Adverse event rates were similar across treatment groups and no significant differences were observed for serum biochemistry and hematology parameters. Differences in levels of AFB(1)-lysine adduct at 1, 3, and 4 months were compared between Placebo and active treatment groups. Although serum AFB(1)-lysine adduct levels were decreased by month 3 for both treatment groups, the Low dose was the only treatment that was significant (p=0.0005). In conclusion, the observed effect in the Low dose treatment group suggests that the use of ACCS100 may be a viable strategy to reduce dietary AFB(1) bioavailability during aflatoxin outbreaks and potentially in populations chronically exposed to this carcinogen

Increased cell-to-cell variation in gene expression in ageing mouse heart.

The accumulation of somatic DNA damage has been implicated as a cause of ageing in metazoa. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by dissociating single cardiomyocytes from fresh heart samples of both young and old mice, followed by global mRNA amplification and quantification of mRNA levels in a panel of housekeeping and heart-specific genes. Although gene expression levels already varied among cardiomyocytes from young heart, this heterogeneity was significantly elevated at old age. We had demonstrated previously an increased load of genome rearrangements and other mutations in the heart of aged mice. To confirm that increased stochasticity of gene expression could be a result of increased genome damage, we treated mouse embryonic fibroblasts in culture with hydrogen peroxide. Such treatment resulted in a significant increase in cell-to-cell variation in gene expression, which was found to parallel the induction and persistence of genome rearrangement mutations at a lacZ reporter locus. These results underscore the stochastic nature of the ageing process, and could provide a mechanism for age-related cellular degeneration and death in tissues of multicellular organisms