Ultrastructural alterations in liver of mice exposed chronically and transgenerationally to aqueous extract of betel nut: Implications in betel nut‐induced carcinogenesis

Abstract

The aqueous extract of betel nut (AEBN) induces the formation of preneoplastic nodules in the liver of Swiss Albino mice and leads to increased predisposition to cancer when administered transgenerationally. The aim of this investigation was to elucidate the alterations in ultrastructure of subcellular organelles in the liver nodules using transmission electron microscopy and to determine whether these alterations have implications in AEBN-induced carcinogenesis. Male and female Swiss Albino mice were exposed to AEBN chronically and transgenerationally at a dose of 2 mg/mL in drinking water for 24 weeks. Extensive polymorphism was noted in nuclear shape and heterochromatin organization. Heterochromatin aggregation and marginalization were observed in the nuclei of chronically exposed mice, whereas transgenerationally exposed mice exhibited dispersion or loss of heterochromatin. The nuclear envelope was disrupted, and the nucleoli were enlarged in chronically exposed mice, whereas in transgenerationally exposed mice the nucleoli were reduced in size or totally absent. The cisternae of the rough endoplasmic reticulum were dilated and disrupted, and a large number of autophagic vesicles were observed in both chronically and transgenerationally exposed mice. Atypical mitochondria that underwent extensive cristolysis and progressively declined in size and number from the chronically exposed mice to the different generations of transgenerationally exposed mice were also observed. Thus, exposure to AEBN resulted in severe loss of ultrastructural integrity of cells in the liver nodules, and the progressive loss of mitochondrial function appeared to play a significant role in increasing the predisposition to cancer of mice exposed transgenerationally to AEBN.