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Hyperplastic, dysplastic and neoplastic lesions associated with a model of carcinogenesis induced by DMBA in the salivary glands of BALB-c mice

International Journal of Molecular Biology: Open Access
Carino S,1 De Moreno de LeBlanc A,2 Aybar Odstrcil AC,1 Castillo SE3


The aim of this work was to develop a mouse model of submandibular salivary gland
carcinogenesis by chemical induction and to perform a revision of the literature on similar
models using the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA). The descriptive
review was carried out on published works in English and Spanish languages, from the period
1977-2023, which included different animal models of chemical carcinogenesis induced by
DMBA in salivary glands. Articles were reviewed in order to analyze the effectiveness
of the carcinogenesis induction. For our model, BALB/c mice were used. Animals were
anesthetized and after surgery to expose the submandibular gland, each mouse was injected
with 2% solution of DMBA in corn oil. Mice were monitored weekly until sacrifice at week
12. The samples were processed with the routine histological methods. The results from the
descriptive review showed that DMBA is mainly administered by Intraglandular injections
into the submandibular glands after surgical exposure, being both pellets and solutions used
for the induction, and rats more common than mice. This revision summarizes the research
results of previous studies and demonstrates which model has greater reproducibility. Our
results showed that one single injection of DMBA directly into the surgically exposed
submandibular gland was an optimal technique to induce the tumor at the desired site.
Edema was observed in the surgical area the first 2 weeks. From week 5, the mice presented
internal hardness and hair loss in the glandular area; 50% of the animals presented palpable
and measurable tumor masses from week 10. Microscopic observations showed that 89% of
the mice developed malignant neoplasms: Carcinomas in situ, micro invasive and invasive
(6/8); sarcomas (1/8) and carcinosarcoma (1/8). Associated lesions were atypical ductal
hyperplasia; periductal fibrosis, sarcomatous stroma. This model marks a difference with
the subcutaneous injection technique, without surgery, which does not allow the carcinogen
to be adequately directed to the gland.


DMBA, salivary glands, cancer, experimental model, mice, histology