AIRmax and AIRmin
mouse strains phenotypically selected for high and low acute inflammatory responsiveness (
AIR) are, respectively, susceptible or resistant to developing
hepatocellular carcinoma (HCC) induced by the chemical
carcinogens urethane and
diethylnitrosamine (DEN). Early
production of TNF-a,
IL-1ß, and
IL-6 in the
liver after DEN
treatment correlated with
tumor development in AIRmax
mice.
Transcriptome analysis of
livers from untreated AIRmax and AIRmin
mice showed specific
gene expression profiles in each line, which might
play a
role in their differential susceptibility to HCC. Linkage
analysis with SNP markers in F2 (AIRmax×AIRmin) intercross
mice revealed two
quantitative trait loci (QTL) in
chromosomes 2 and 9, which are significantly associated with the number and progression of
urethane-induced
liver tumors. An independent linkage
analysis with an intercross
population from A/J and C57BL/6J inbred
mice mapped regions in
chromosomes 1 and 7 associated with the progression of
urethane-induced
liver tumors, evidencing the heterogeneity of HCC genetic control.