N-Nitrosomorpholine-induced oncocytic transformation in rat endocrine organs

Abstract

Background: N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats.

Methods: Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised.

Results: There was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal.

Conclusions: We showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.

Keywords: Endocrine disrupting chemical; Endocrine disruptors; Endocrine gland neoplasms; Nitroso compounds; Oncocyte.

Fig. 1

a Normal adrenal gland layers (inner to outer layer) (H&E, × 200). b Oncocytic cell groups with well-defined cell borders, deeply eosinophilic, granular cytoplasm, small round nuclei (H&E, × 200)

Fig. 2

a Thyroid parenchyma composed of normal follicle epithelial cells (H&E, × 400). b Oncocytes with large size, prominent cell borders, eosinophilic, and granular cytoplasm on thyroid sections (H&E, × 400)

Fig. 3

a Normal pituitary tissue showing relative cellular monomorphism with a single cell type (H&E, × 400). b Oncocytic cells scattered in the pituitary parenchyma (H&E, × 400)

Fig. 4

a Normal pancreatic parenchyma (H&E, × 400). b Oncocytic cells located between acinar cells and endocrine cells (H&E, × 400)