Measuring microenvironment mechanical stress of rat liver during diethylnitrosamine induced hepatocarcinogenesis by atomic force microscope.

We developed a highly sensitive method to detect liver tissue stiffness with atomic force microscopy (AFM), and investigated the physical features of hepatocarcinogenesis. Wistar rats received weekly intraperitoneal injections of diethylnitrosamine (DEN) or saline (control) followed by a 2-week wash-out period. Liver samples were harvested at 10, 14, or 18 weeks for pathological examination and stress detection. Previously normal liver tissues developed fibrosis and carcinoma after DEN administration. Although the elastic modulus (E) values of the normal (saline; 0.18 +/- 0.04 MPa), fibrotic (8 weeks DEN; 0.25 +/- 0.06 MPa) and cirrhotic (12 weeks DEN; 0.39 +/- 0.06 MPa) tissues were significantly different, there was no significant difference between the E values of the cirrhotic and the hepatic cell carcinoma (16 weeks DEN; 0.42 +/- 0.07 MPa) tissues. Thus, tissue stiffness quantitatively increases during hepatocarcinogenesis, and AFM can be used to sensitively and precisely detect liver stiffness at the microscopic level.