Reference SummaryHayashi S, Toxicol Pathol 2001 Jul-Aug;29(4):422-9

Title

 High frequency of ras mutations in forestomach and lung tumors of B6C3F1 mice exposed to 1-amino-2,4-dibromoanthraquinone for 2 years.

Authors

 Hayashi S; Hong HH; Toyoda K; Ton TV; Devereux TR; Maronpot RR; Huff J; Sills RC

Journal

 Toxicol Pathol

Volume

 29

Issue

 4

Year

 2001

Pages

 422-9

Abstract

 1-Amino-2,4-dibromoanthraquinone (ADBAQ) is an anthraquinone-derived vat dye, and a potent carcinogen in laboratory animals. In a 2-year study with dietary exposure to 10,000 or 20,000 ppm ADBAQ, increased incidence of forestomach and lung tumors were observed in B6C3F1 mice. The present study indentified genetic alterations in H-ras and K-ras proto-oncogenes in ADBAQ-induced tumors. Point mutations in ras proto-oncogenes were identified by restriction fragment length polymorphism, single-stranded conformational polymorphism analysis and cycle sequencing of polymerase chain reaction-amplified DNA isolated from paraffin-embedded squamous cell papillomas and carcinomas in the forestomach, and alveolar/bronchiolar adenomas and carcinomas in the lung. A higher frequency of ras mutations was identified in ADBAQ-induced forestomach (23/32, 72%) and lung tumors (16/23, 70%) than in spontaneous forestomach (4/11, 36%) and lung tumors (26/86, 30%). H-ras codon 61 CTA mutations were detected in (4/8, 50%) ADBAQ-induced forestomach squamous cell papillomas and (10/24, 42%) squamous cell carcinomas, but not in the spontaneous forestomach tumors examined. H-ras codon 61 CGA mutation (6/24, 25%) was also detected in ADBAQ-induced forestomach squamous cell carcinomas. K-ras codon 61 A to T transversions and A to G transitions were prominent in ADBAQ-induced lung alveolar/bronchiolar adenomas and alveolar/bronchiolar carcinomas. The major finding of A to T transversions or A to G transitions in forestomach and lung tumors suggests that ADBAQ or its metabolites target adenine bases in the ras proto-oncogenes and that these mutations play a dominant role in multi-organ

Links

 J:71718 – MGI References
11560247 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(C57BL/6 x C3H)F1 Forestomach squamous cell carcinoma
  • 1-amino-2,4-dibromoanthraquinone
 Forestomach

observed - 54
(C57BL/6 x C3H)F1 Forestomach squamous cell carcinoma Forestomach

0 - 4
(C57BL/6 x C3H)F1 Forestomach squamous cell papilloma
  • 1-amino-2,4-dibromoanthraquinone
 Forestomach

observed - 26
(C57BL/6 x C3H)F1 Forestomach squamous cell papilloma Forestomach

0
(C57BL/6 x C3H)F1 Forestomach tumor
  • 1-amino-2,4-dibromoanthraquinone
 Forestomach

observed
(C57BL/6 x C3H)F1 Forestomach tumor Forestomach

observed
(C57BL/6 x C3H)F1 Forestomach tumor - squamous Forestomach

0 - 4
(C57BL/6 x C3H)F1 Forestomach tumor - squamous
  • 1-amino-2,4-dibromoanthraquinone
 Forestomach

37.25 - 68
(C57BL/6 x C3H)F1 Lung adenoma
  • 1-amino-2,4-dibromoanthraquinone
 Lung

observed - 52.48
(C57BL/6 x C3H)F1 Lung adenoma Lung

8 - 14
(C57BL/6 x C3H)F1 Lung carcinoma Lung

0 - 6
(C57BL/6 x C3H)F1 Lung carcinoma
  • 1-amino-2,4-dibromoanthraquinone
 Lung

0 - 7.84
(C57BL/6 x C3H)F1 Lung squamous cell papilloma
  • 1-amino-2,4-dibromoanthraquinone
 Lung

observed
(C57BL/6 x C3H)F1 Lung tumor Lung

observed - 20
(C57BL/6 x C3H)F1 Lung tumor
  • 1-amino-2,4-dibromoanthraquinone
 Lung

observed - 54.9