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

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Abstract

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