Open Access

Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c Trp53 knockout mice

  • Authors:
    • Yukino Machida
    • Toshio Imai
  • View Affiliations

  • Published online on: August 16, 2021     https://doi.org/10.3892/ol.2021.12999
  • Article Number: 738
  • Copyright: © Machida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemical carcinogens, such as 7,12‑dimethylbenz[a]anthracene (DMBA) and 2‑amino‑1‑methyl‑6‑phenylimidazo(4,5‑b)pyridine (PhIP), are known to induce mammary carcinomas in mice and rats. In the present study, the phenotypic and genotypic characteristics of carcinogen‑induced mammary carcinogenesis in heterozygous BALB/c tumor protein p53 (Trp53) knockout mice were examined with reference to published data surrounding human breast cancer. A significantly accelerated induction of mammary carcinomas was observed following a single dose of DMBA (50 mg/kg of body weight at 7 weeks of age), and a modest acceleration was induced by PhIP (50 mg/kg of body weight) administered by gavage 6 times/2 weeks from 7 weeks of age. DMBA‑induced mammary carcinomas were histopathologically characterized by distinct biphasic structures with luminal and myoepithelial cells, as well as a frequent estrogen receptor expression, and PhIP‑induced carcinomas with solid/microacinar structures consisted of pleomorphic cells. Of note, DMBA‑induced mammary carcinomas were characterized by a HRas proto‑oncogene (Hras) mutation at codon 61, and gene/protein expression indicating MAPK stimulation. PhIP‑induced lesions were suspected to be caused by different molecular mechanisms, including Wnt/β‑catenin signaling and/or gene mutation‑independent PI3K/AKT signaling activation. In conclusion, the present mouse mammary carcinogenesis models, induced by a combination of genetic and exogenous factors, may be utilized (such as the DMBA‑induced model with Trp53 gene function deficiency as a model of adenomyoepithelioma, characterized by distinct biphasic cell constituents and Hras mutations), but PhIP‑induced models are required to further analyze the genetic/epigenetic mechanisms promoting mammary carcinomas.
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October-2021
Volume 22 Issue 4

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Spandidos Publications style
Machida Y and Machida Y: Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c <em>Trp53</em> knockout mice. Oncol Lett 22: 738, 2021
APA
Machida, Y., & Machida, Y. (2021). Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c <em>Trp53</em> knockout mice. Oncology Letters, 22, 738. https://doi.org/10.3892/ol.2021.12999
MLA
Machida, Y., Imai, T."Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c <em>Trp53</em> knockout mice". Oncology Letters 22.4 (2021): 738.
Chicago
Machida, Y., Imai, T."Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c <em>Trp53</em> knockout mice". Oncology Letters 22, no. 4 (2021): 738. https://doi.org/10.3892/ol.2021.12999