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Nicotine caused cancer in mice

Muscle sarcomas and alopecia in A/J mice chronically treated with nicotine

  • ·        Valentin Galitovskiya,
  • ·        Alexander I. Chernyavskya,
  • ·        Robert A. Edwardsb,
  • ·        a Department of Dermatology, University of California, Irvine, CA, USA
  • ·        b Department of Pathology, University of California, Irvine, CA, USA
  • ·        c Cancer Center and Research Institute, University of California, Irvine, CA, USA
  • ·        Received 1 December 2011. Accepted 24 March 2012. Available online 12 April 2012.
  • ·        Abstract
  • ·        Aims
  • ·        To evaluate the pathobiologic effects of long-term treatment with nicotine of A/J mice susceptible to tobacco-induced lung carcinogenesis.
    • ·        Main methods
    • ·        Experimental group of mice received subcutaneous injections of the LD50 dose of (−)nicotine hydrogen tartrate of 3 mg/kg/day, 5 days per week for 24 months, and control group received the vehicle phosphate-buffered saline.
      • ·        Key findings
      • ·        Nicotine treated mice, 78.6%, but none of control of mice, developed neoplasms originating from uterus or skeletal muscle. Examination of the uterine neoplasms revealed leiomyosarcomas, composed of whorled bundles of smooth-muscle like cells with large and hyperchromatic nuclei. Sections of the thigh neoplasms revealed densely cellular tumors composed of plump spindle cells, with occasional formation of ‘strap’ cells, containing distorted striations. Both neoplasms were positive for desmin staining. A solitary pulmonary adenoma with papillary architecture also occurred in one nicotine treated mouse. Experimental mice also developed transient balding starting as small patches of alopecia that progressed to distinct circumscribed areas of complete hair loss or large areas of diffuse hair loss.


We demonstrate for the first time that chronic nicotine treatment can induce the development of muscle sarcomas as well as transient hair loss. These findings may help explain the association of childhood rhabdomyosarcoma with parental smoking and earlier onset of balding in smokers. It remains to be determined whether the pathobiologic effects of nicotine result from its receptor mediated action and/or its tissue metabolites cotinine and N’-nitrosonornicotine, or toxic effects of reactive oxygen species activated due to possible intracellular accumulation of nicotine.


  • ·        A/J mice;
  • ·        nicotine;
  • ·        leiomyosarcoma;
  • ·        rhabdomyosarcoma;
  • ·        alopecia
  • ·        Figures and tables from this article:
    • ·
    • ·        Fig. 1. Nicotine-induced muscle sarcomas in A/J mice.A, B: Uterine leiomyosarcoma. C, D:Rhabdomyosarcoma of the quadriceps muscle. E. Immunofluorescent analysis of rhabdomyosarcoma with anti-desmin antibody showing intense punctate cytoplasmic staining in the neoplastic cells (at left) and diffuse subsarcolemmal staining in the adjacent normal striated muscle (at right), serving as an internal positive control.
    • ·
    • ·        Fig. 2. Hair loss in A/J mice. Patchy (A, B) and diffuse (C) areas of alopecia observed at 10 months of treatment with nicotine. D: The representative differences of hair follicle numbers in the areas of diffuse alopecia, compared to the same cutaneous region of control mouse. Results were computed in 10 microscopic fields of horizontal sections of trunkal skin at magnification x4, and presented as mean ± SD per 1 mm ²; p = 0.003.

Corresponding author at: University of California Irvine, 134 Sprague Hall, Irvine, CA 92697, USA. Tel.: + 1 949 824 2713; fax: + 1 949 824 2993.

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