Reference SummaryDwyer-Nield LD, Int J Cancer 2010 Jan 1;126(1):125-32
Title |
Epistatic interactions govern chemically-induced lung tumor susceptibility and Kras mutation site in murine C57BL/6J-ChrA/J chromosome substitution strains. | ||||||||||||||||||||||||||||
Authors |
Dwyer-Nield LD; McQuillan J; Hill-Baskin A; Radcliffe RA; You M; Nadeau JH; Malkinson AM | ||||||||||||||||||||||||||||
Journal |
Int J Cancer | ||||||||||||||||||||||||||||
Volume |
126 | ||||||||||||||||||||||||||||
Issue |
1 | ||||||||||||||||||||||||||||
Year |
2010 | ||||||||||||||||||||||||||||
Pages |
125-32 | ||||||||||||||||||||||||||||
Abstract |
Cancer susceptibility results from interactions between sensitivity and resistance alleles. We employed murine chromosome substitution strains to study how resistance alleles affected sensitive alleles during chemically-induced lung carcinogenesis. The C57BL/6J-Chr#(A/J) strains, constructed by selectively breeding sensitive A/J and resistant C57BL/6J (B6) mice, each contain one pair of A/J chromosomes within an otherwise B6 genome. Pas1, the major locus responsible for this differential strain response to urethane carcinogenesis, resides on Chr 6, but C57BL/6J-Chr6(A/J) mice (hereafter CSS-6) developed few tumors following a single urethane injection, which demonstrates epistatic interactions with other B6 alleles. CSS6 mice developed dozens of lung tumors after chronic urethane exposure, however, indicating that these epistatic interactions could be overcome by repeated carcinogen administration. Unlike A/J, but similar to B6 mice, CSS6 mice were resistant to lung carcinogenesis induced by 3-methylcholanthrene (MCA). Tumor multiplicity increased if BHT administration followed urethane exposure, showing that a Chr 6 gene(s) regulates sensitivity to chemically-induced tumor promotion. Unlike A/J tumors (predominantly codon 61 A-->T transversions), Kras mutations in tumors induced by urethane in CSS-6 mice were similar to B6 tumors (codon 61 A-->G transitions). DNA repair genes not located on Chr 6 may determine the nature of Kras mutations. CSS-6 mice are a valuable resource for testing the ability of candidate genes to modulate lung carcinogenesis. | ||||||||||||||||||||||||||||
Links |
J:157052 – MGI References 19609923 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6J | Lung tumor |
|
Lung |
observed - 100 |
|
C57BL/6J | Lung tumor |
|
Lung |
100 |
|
C57BL/6J-Chr 4A/J/Na | Lung tumor |
|
Lung |
24 |
|
C57BL/6J-Chr 6A/J/Na | Lung tumor |
|
Lung |
observed - 100 |
|
C57BL/6J-Chr 6A/J/Na | Lung tumor |
|
Lung |
observed |
|
C57BL/6J-Chr 6A/J/Na | Lung tumor |
|
Lung |
observed |
|
C57BL/6J-Chr 6A/J/Na | Lung tumor |
|
Lung |
observed |
|
C57BL/6J-Chr 9A/J/Na | Lung tumor |
|
Lung |
48 |
|
C57BL/6J-Chr 10A/J/Na | Lung tumor |
|
Lung |
37 |
|
C57BL/6J-Chr 11A/J/Na | Lung tumor |
|
Lung |
88 - 100 |
|
C57BL/6J-Chr 14A/J/Na | Lung tumor |
|
Lung |
22 |
|
C57BL/6J-Chr 15A/J/Na | Lung tumor |
|
Lung |
58 |
|
C57BL/6J-Chr 17A/J/Na | Lung tumor |
|
Lung |
62 |
|
C57BL/6J-Chr 18A/J/Na | Lung tumor |
|
Lung |
50 |
|
C57BL/6J-Chr 19A/J/Na | Lung tumor |
|
Lung |
64 |
|
C57BL/6J-Chr YA/J/Na | Lung tumor |
|
Lung |
52 |
|
A/J | Lung tumor |
|
Lung |
observed - 100 |
|
A/J | Lung tumor |
|
Lung |
observed |
|
A/J | Lung tumor |
|
Lung |
observed |
|
(C57BL/6J x C57BL/6J-Chr 6A/J/NaJ)F1 | Lung tumor |
|
Lung |
100 |