EXPERIMENTAL-STUDY ON THE ROLE OF OSTEOCLASTS AND FREE-RADICALS IN THE MANDIBULAR INVASION OF VX2 CARCINOMA IN JAPANESE WHITE-RABBITS

Oxygen-derived free radicals are stimulators of bone resorption in vit ro and in vivo, We hypothesized that oxygen derived free radicals or r eactive oxygen species (ROS) generated around bone matrix invaded by c ancer cells might be associated with the activation or formation of os teoclasts in bone metastasis, and thus the administration of an ROS sc avenger or a free-radical scavenger might control osteoclastic bone de struction in tumor metastasis. We examined the ability of VX2 carcinom a cells to generate superoxide anion (O-2(-)) as well as the effects o f the O-2(-) scavenger superoxide dismutase (SOD) and the hydrogen per oxide (H2O2) scavenger catalase (CAT) on the activation and formation of osteoclasts in VX2 carcinoma tissue of rabbits, VX2 carcinoma cells generated more O-2(-) than tartrate-resistant acid phosphatase-positi ve (TRAP+) cells, The TRAP activity from TRAP+ cells in the presence o f VX2 carcinoma cells was higher than that from TRAP+ cells in the abs ence of the carcinoma cells, The addition of SOD but not of CAT into t he incubation medium inhibited the TRAP activity from TRAP+ cells in t he presence or absence of VX2 carcinoma cells, Similar inhibitory effe cts were also observed with SOD plus CAT on TRAP+ cells in the presenc e or absence of carcinoma cells, Intravenous administration of SOD and SQD plus CAT, but not of CAT, caused a decrease in the number of oste oclasts in mandibles implanted with VX2 carcinoma cells, and showed a predominant occupation by osteoclasts with poorly developed ruffled bo rders in lesions of bone resorption, In contrast, the administration o f CAT, but not of SOD and SOD plus CAT, decreased the more mature form s of osteoclasts in implanted mandibles, From the results obtained, it is suggested that O-2(-) may stimulate bone resorption by increasing the activity and number of osteoclasts, and H2O2 may stimulate resorpt ion by enhancing the formation of mature osteoclasts in tumor metastas is. The administration of same ROS or free-radical scavengers to patie nts with cancer may provide a defense against bone destruction in bone metastatic lesions. (C) 1997 by Elsevier Science Inc.