Reference SummarySpalding JW, Toxicol Sci 1999 Jun;49(2):241-54

Title

 Development of a transgenic mouse model for carcinogenesis bioassays: evaluation of chemically induced skin tumors in Tg.AC mice.

Authors

 Spalding JW; French JE; Tice RR; Furedi-Machacek M; Haseman JK; Tennant RW

Journal

 Toxicol Sci

Volume

 49

Issue

 2

Year

 1999

Pages

 241-54

Abstract

 Transgenic rodent models have emerged as potentially useful tools in the assessment of drug and chemical safety. The transgenic Tg.AC mouse carries an inducible v-Ha-ras oncogene that imparts the characteristic of genetically initiated skin to these animals. The induction of epidermal papillomas in the area of topically applied chemical agents, for duration of not more than 26 weeks, acts as a reporter phenotype that defines the activity of the test article. We describe here the activity of six chemicals that have been previously characterized for activity in the standard 2-year bioassay conducted by the National Toxicology Program (NTP). Homozygous female Tg.AC mice were treated with benzene (BZ), benzethonium chloride (BZTC), o-benzyl-p-chlorophenol (BCP), 2-chloroethanol (2-CE), lauric acid diethanolamine (LADA) and triethanolamine (TEA). BZ and LADA induced skin papillomas in a dose-dependent manner, while BCP induced papillomas only at the highest dose. BZTC, 2-CE, and TEA exhibited no activity. The correspondence of chemical activity in Tg.AC mice with that in the 2-year bioassay was high. A comparison of responsiveness to BZ and LADA was made between hemizygous and homozygous female Tg.AC mice. Both genotypes appear to be equally sensitive to maximum doses of active compounds. The results reported here indicate that the Tg.AC transgenic mouse model can discriminate between carcinogens and noncarcinogens and that both mutagenic and nonmutagenic chemicals can be detected. These studies provide support for the adjunctive use of the Tg.AC transgenic mouse skin tumor model in drug and chemical safety assessment and for the prediction of the carcinogenic potential of chemicals.

Links

 J:59627 – MGI References
10416269 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma Skin

0 - 60
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • benzene
 Skin

70 - 100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Skin

observed - 100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • benzethonium (BZTC)
 Skin

0 - 40
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • 2-chloroethanol (2-CE)
 Skin

0 - 33.3
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • o-benzyl-p-chlorophenol (BCP)
 Skin

7.7 - 84.2
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • triethanolamine (TEA)
 Skin

21.1 - 38.5
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Skin

observed - 100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • benzene
 Skin

92.9 - 100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma Skin

5.3 - 5.6
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • lauric acid diethanolamine (LDA)
 Skin

6.7 - 93.3
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Skin papilloma
  • lauric acid diethanolamine (LDA)
 Skin

20 - 86.7
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • benzene
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • benzethonium (BZTC)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • 2-chloroethanol (2-CE)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • o-benzyl-p-chlorophenol (BCP)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • triethanolamine (TEA)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • lauric acid diethanolamine (LDA)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • benzene
 Bone - Jaw

observed
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed Tooth odontoma
  • lauric acid diethanolamine (LDA)
 Bone - Jaw

observed