Chemically Induced Hepatocellular Carcinoma and Stages of Development with Biochemical and Genetic Modulation: A Special Reference to Insulin-Like-Growth Factor II and Raf Gene Signaling

Abstract

The liver, the largest organ in the body, predominantly functions as a biochemical laboratory where metabolism takes place. It has both endocrine and exocrine functions; and is also involved in numerous metabolic activities and acting as a storage depot. Once the nutritional substances and other chemicals such as drugs, carcinogens etc. reach in liver, they are metabolized by hepatic enzymes. The organ is located on the right side of the abdomen just beneath the diaphragm in human. Liver is a solid organ consisting of several lobes. Each lobe is constituted with numerous lobules which are in general hexagonal in shape (Figure 1). The center of each lobule is occupied by the central vein and the periphery of the lobule is delineated by a close arrangement of hepatic artery, portal vein, and bile duct; called “portal triads”. The portal triads appear at the vertices of the hexagonal lobules. The vessels generated from the portal triads ramify and distribute along the sides of the lobule, and open into the sinusoids which have thin epithelial lining, a discontinuous layer of fenestrated endothelial cells. The liver has different types of cells. Oval cells are generally found near the portal triad. This rare cell-type has been claimed as hepatic stem cells by some researchers (Zamule et al., 2011). However, the major cell-type in liver is the polygonal hepatic parenchymal cells (hepatocytes). Hepatic lobules are made up of more than 80% hepatocytes which have an average size of 25  and occupy 70-90% of liver mass, depending on the species. They have clear cell membrane; sometimes with two nuclei. They have large deposits of glycogen, often with lipid droplets and basophilic materials. They also contain other cellular organelles such as mitochondria, rough endoplasmic reticulum (granular) and smooth endoplasmic reticulum (agranular), golgi apparatus, and lysosomes. The hepatocytes are arranged in stacks of anastomosing plates, separated by an anastomosing