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

Abstract

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 microg, which resulted in sarcomas-induction in 0, 62, and 94% of rats. Male SD rats were injected with DMBA 500 microg 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.

Proliferative and Non-Proliferative Lesions of the Rat and Mouse Soft Tissue, Skeletal Muscle and Mesothelium

“…Sarcomas can also be induced in rodents by injection of oncogenic viruses and carcinogens such as 7,12-dimethylbenz[ a ]anthracene as well as repeated injection of a diverse range of non-genotoxic chemicals ( 19 Chesterman et al 1966; 44 Grasso and Goldberg 1966a, 45 b; 58 Hooson et al 1973; 107 Taguchi et al 2006). Implantation into rodents of impervious solid foreign bodies made from a wide variety of materials also induces sarcomas in the surrounding tissues.…”

Rhabdomyosarcomas: an overview on the experimental animal models

“…Polycyclic aromatic hydrocarbons are implicated in the aetiology of human cancer due to exposure to cigarette smoke, urban air, pollution, coal combustion and certain occupational situations . For example, exposure to 7,12‐dimethylbenz[a]anthracene elicited RMS formation in Zebrafish, although at low incidence , whereas the same molecule was recently shown more effective in causing RMS in male Sprague–Dawley rats . Also, RMS was detected in mice treated with benzo[a]pyrene , even in association with nickel compounds .…”

The generation and use of animal models of osteosarcoma in cancer research

“…Injecting chemical agents into the muscles of animals at a constant concentration can also induce OS, but usually takes a long time (typically >40 weeks). 45 These chemicals include beryllium zinc silicate, aflatoxin B1, arsenite, 7,12-dimethylbenzanthracene, 4-hydroxyaminoquinoline-1-oxide, beryllium oxide, methylcholanthracene, N-hydroxyl, copper compound of 2-acetamide fluorene, and diethylnitrosamine. 46 , 47 However, the chemical-induced cancer model has low reproducibility, and the chemicals can be harmful to researchers.…”