Reference SummaryDrinkwater NR, Carcinogenesis 1986 Oct;7(10):1701-7

Title

Genetic control of hepatocarcinogenesis in C57BL/6J and C3H/HeJ inbred mice.

Authors

Drinkwater NR; Ginsler JJ

Journal

Carcinogenesis

Volume

7

Issue

10

Year

1986

Pages

1701-7

Abstract

Treatment of newborn male C3H/HeJ mice with N,N-diethyl-nitrosamine (DEN) or N-ethyl-N-nitrosourea (ENU) resulted in the induction of hepatocellular adenomas and carcinomas with a mean number of tumors per animal that was approximately 20- to 50-fold higher than that for similarly treated C57BL/6J male mice. We used two methods to study the genetic basis for this difference in susceptibility to liver tumor induction. Analysis of DEN-induced liver tumor multiplicities as a quantitative genetic trait in segregating crosses between C3H/HeJ and C57BL/6J mice indicated that allelic differences for at least two loci contributed to the higher sensitivity to hepatocarcinogenesis of C3H/HeJ mice relative to C57BL/6J mice. However, a single locus, which we have denoted Hcs (hepatocarcinogen sensitivity), was responsible for approximately 85% of the difference in susceptibility. The C57BL/6J and C3H/HeJ alleles at this locus were semi-dominant. This result was confirmed by analysis of hepatocarcinogenesis by ENU in BXH (C57BL/6J X C3H/HeJ) recombinant inbred mice. Four of the nine recombinant inbred strains studied were highly susceptible to the induction of liver tumors by ENU, three of the strains exhibited the resistant phenotype of the C57BL/6J parent, and two of the strains were of intermediate sensitivity to hepatocarcinogenesis. Newborn male C3H/HeJ and C57BL/6J mice did not significantly differ in the extent of ethylation of hepatic DNA, or in the relative levels of N-7-ethylguanine or O6-ethylguanine after treatment with [1-14C]DEN.

Links

J:8421 – MGI References
3757172 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
BXH10/TyJ Leukocyte - Lymphocyte lymphoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Thymus

4.55

BXH19/TyJ Leukocyte - Lymphocyte lymphoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Thymus

3.33

BXH3/TyJ Liver - Bile duct cholangiocarcinoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver - Bile duct

4.35

C57BL/6J Liver adenoma
  • tricaprylin (trioctanoin)
Liver

0

C57BL/6J Liver adenoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C3H/HeJ Liver adenoma
  • tricaprylin (trioctanoin)
Liver

0

C3H/HeJ Liver adenoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

(C57BL/6J x C3H/HeJ)F1/J Liver adenoma
  • tricaprylin (trioctanoin)
Liver

0

(C57BL/6J x C3H/HeJ)F1/J Liver adenoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C57BL/6J Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
Liver

0

C57BL/6J Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C3H/HeJ Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
Liver

0

C3H/HeJ Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

(C57BL/6J x C3H/HeJ)F1/J Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
Liver

0

(C57BL/6J x C3H/HeJ)F1/J Liver hepatocellular carcinoma
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C57BL/6J Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
Liver

0

C57BL/6J Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C3H/HeJ Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
Liver

0

C3H/HeJ Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

(C57BL/6J x C3H/HeJ)F1/J Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
Liver

0

(C57BL/6J x C3H/HeJ)F1/J Liver preneoplastic lesion
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

observed

C57BL/6J Liver tumor
  • tricaprylin (trioctanoin)
Liver

0

C57BL/6J Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

29.73 - 76.19

C3H/HeJ Liver tumor
  • tricaprylin (trioctanoin)
Liver

0

C3H/HeJ Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

100

(C57BL/6J x C3H/HeJ)F1/J Liver tumor
  • tricaprylin (trioctanoin)
Liver

0

(C57BL/6J x C3H/HeJ)F1/J Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

92.31 - 100

(C57BL/6J x C3H/HeJ)F1/J x C57BL/6J Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

85.81

(C57BL/6J x C3H/HeJ)F1/J x C3H/HeJ Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

100

(C57BL/6J x C3H/HeJ)F2/J Liver tumor
  • tricaprylin (trioctanoin)
  • diethylnitrosamine (DEN)
Liver

91.86

C57BL/6J Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

26.92

C3H/HeJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

95

BXH3/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

100

BXH4/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

89.47

BXH6/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

75

BXH7/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

100

BXH8/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

96

BXH9/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

100

BXH10/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

81.82

BXH14/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

50

BXH19/TyJ Liver tumor
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Liver

76.67

C57BL/6J Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

C3H/HeJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH3/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH4/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH6/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH7/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH8/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH9/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH10/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH14/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed

BXH19/TyJ Lung adenoma
  • tricaprylin (trioctanoin)
  • 1-ethyl-1-nitrosourea (ENU)
Lung

observed