Title: A single neonatal exposure to aflatoxin b1 induces prolonged genetic damage in two loci of mouse liver.
Authors: Wattanawaraporn, Roongtiwa; Woo, Leslie L; Belanger, Crystal; Chang, Shiou-Chi; Adams, Jillian E; Trudel, Laura J; Bouhenguel, Jason T; Egner, Patricia A; Groopman, John D; Croy, Robert G; Essigmann, John M; Wogan, Gerald N
Published In Toxicol Sci, (2012 Aug)
Abstract: Aflatoxin B (1) (AFB(1)) is a risk factor for hepatocellular carcinoma in humans. Infant, but not adult, mice are sensitive to AFB(1)-induced liver carcinogenesis; a single dose during the neonatal period leads to hepatocellular carcinoma in adulthood. Earlier work defined the mutational spectrum in the gpt gene of gpt delta B6C3F1 mice 3 weeks after exposure to aflatoxin. In the present study, we examined the gpt spectrum 10 weeks postdosing and expanded the study to examine, at 3 and 10 weeks, the spectrum at a second locus, the red/gam genes of the mouse λEG10 transgene. Whereas the gpt locus is typically used to define local base changes, the red/gam genes, via the Spi(-) assay, often are used to detect more global mutations such as large deletions and rearrangements. Three weeks after dosing with AFB(1), there was a 10-fold increase over the control in the Spi(-) mutant fraction (MF) in liver DNA; after 10 weeks, a further increase was observed. The MF in the gpt gene was also increased at 10 weeks compared with the MF at 3 weeks. No gender-specific differences were found in the Spi(-) or gpt MFs. Whereas Spi(-) mutations often signal large genetic changes, they did not in this specific case. The Spi(-) spectrum was dominated by GC to TA transversions, with one exceptionally strong hotspot at position 314. Using two genetic loci, the data show a strong preference for the induction of GC to TA mutations in mice, which is the dominant mutation seen in people exposed to aflatoxin.
PubMed ID: 22539618
MeSH Terms: Aflatoxin B1/administration & dosage; Aflatoxin B1/toxicity*; Animals; Animals, Newborn; Base Sequence; DNA Primers; Dose-Response Relationship, Drug; Liver/drug effects*; Male; Mice; Mice, Inbred C3H; Polymerase Chain Reaction