title: A single neonatal exposure to aflatoxin b1 induces prolonged genetic damage in two loci of mouse liver.
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.
authors.affiliation: Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Roongtiwa
authors.initials: R
authors.lastname: Wattanawaraporn
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Woo
authors.forename: Crystal
authors.initials: C
authors.lastname: Belanger
authors.forename: Shiou-Chi
authors.initials: SC
authors.lastname: Chang
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Adams
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Trudel
authors.forename: Jason T
authors.initials: JT
authors.lastname: Bouhenguel
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Egner
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
authors.forename: Robert G
authors.initials: RG
authors.lastname: Croy
authors.forename: John M
authors.initials: JM
authors.lastname: Essigmann
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Wogan
mesh_terms: D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D016604:Aflatoxin B1