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Induction of Sarcomas by a Single Subcutaneous Injection of 7,12-Dimethylbenz[a]anthracene into Neonatal Male Sprague–Dawley Rats: Histopathological and Immunohistochemical Analyses

¹ Department of Tumor Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
² Department of Pathology, Labour Welfare Corporation Kumamoto Rosai Hospital, Kumamoto 866-8533, Japan
³ Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd. (SNBL), Kagoshima 890-0081, Japan
⁴ Department of Clinical Pathology, Kagoshima Prefectural Oshima Hospital, Kagoshima 894-0015, Japan

Correspondence: Address correspondence to: Hiroki Yoshida, M.D., Department of Tumor Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan; e-mail:ichibyo{at}m3.kufm.kagoshima-u.ac.jp

Animal experiments have shown that carcinogenicity of chemicals is higher in fetal or neonatal periods than adult. We investigated sensitivities to a carcinogen in peri-neonatal rats with a model of sarcomas-induction by a subcutaneous injection of chemo-carcinogen that has rarely done in neonatal rats. Neonatal male SD rats were injected with 7,12-DMBA 10, 100, and 500 µg, which resulted in sarcomas-induction in 0, 62, and 94% of rats. Male SD rats were injected with DMBA 500 µg at 0, 3, 7, 14, and 21 days, which resulted in sarcomas-induction in 94, 70, 64, 50, and 44% of rats. Although the induced sarcomas were occasionally in mixed morphological feature as previous reports for sarcomas of rat, each was immunohistochemically in almost monotonous pattern, and classification was feasible. The incidence of rhabdomyosarcomas was higher in rats neonatally injected with a higher dose of DMBA than a lower dose, and in rats injected at peri-neonatal periods than later periods. In histological observations for the site of injection before overt sarcomas develop, clusters of atypical mesenchymal cells emerged as previous studies, but also those were immunohistochemically differentiated into rhabdomyocytes and other mesenchymal cells. We consider these findings may contribute a little to elucidation of process of sarcomas-induction in rats.

Key Words: Polycyclic aromatic hydrocarbon • histology • immunohistochemistry • rhabdomyosarcoma • presarcomatous lesion • rhabdomyoblast • myofibroblast

Abbreviations: DMBA, 7,12-Dimethylbenz[a]anthracene • PAHs, polycyclic aromatic hydrocarbons • SD, Sprague-Dawley

Toxicologic Pathology, Vol. 34, No. 4, 336-347 (2006)
DOI: 10.1080/01926230600773966


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