Histomorphologic and morphometric changes in minor salivary glands of the rat tongue during 4-nitroquinoline-1-oxide-induced carcinogenesis

Abstract 

4-Nitroqinoline-1-Oxide (4NQO)-induced tongue carcinogenesis in rats is considered to be a preferred model for study of oral squamous cell carcinoma. Aim of study was to investigate histomorphologic and morphometric 4NQO-induced changes in tongue minor salivary glands. Histopathological examinations of serous and mucous acini and ducts of tongue salivary glands of 26 Wistar-derived rats were performed after 14 (T₁), 22 (T₂) and 28 (T₃) weeks of 0.001% 4NQO administration in drinking water and compared with nine controls. Histomorphological findings were recorded as normal/abnormal acini and as normal/dysplastic ducts. Morphometrical results were expressed as volume fraction (Vv%) of each of the components. Morphometric and histomorphologic changes in the salivary glands were evident only at T₃ and they included a significant (P=0.008) decrease in the Vv of the serous acini compared with the control group accompanied by abnormal acini (Vv=18%). In contrast, mucous acini and ducts did not demonstrate significant changes. In one case (3.8%), dysplastic ducts were found adjacent to islands of invasive squamous cell carcinoma of tongue mucosa origin. The change in saliva composition expected after considerable damage of the serous glands could create a microenvironment that makes entrapment of the carcinogen easier and prolongs exposure of tongue epithelium. Furthermore, the dysplastic changes in the ducts can serve as a reservoir of carcinoma cells. These observations should be considered in human patients diagnosed with oral dysplasia or carcinoma, especially involving the tongue and floor of mouth.

Keywords:  4NQO-Carcinogenesis, Rats, Tongue, Acini, Ducts, Dysplasia