Increased telomerase activity is not directly related to metastatic potential in rat transplantable osteosarcomas Akira Kido a,b , Toshifumi Tsujiuchi a , Masahiro Tsutsumi a , Makoto Takahama a , Yoshizumi Miyauchi b , Yoshio Mii b , Susumu Tamai b , Yoichi Konishi a, * a Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan b Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan Received 7 March 1997; accepted 24 March 1997 Abstract Previously, we reported the establishment of two transplantable osteosarcomas in rats, one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1-oxide (4-HAQO), and another which developed spontaneously, and their subdivision into four lines with high and low metastatic potential to the lung. In the present study, activation of telomerase was investigated by the telomeric repeat amplification protocol (TRAP) assay followed by densitometric quantification. Telomer- ase activity was found to be elevated in all four lines without any link to the metastatic potential. Thus the spontaneous osteosarcoma (SOS) and derived metastatic lesions (S-SLM) demonstrated a 20.1–23.5-fold increase and the chemical carcinogen (4HAQO)-induced osteosarcoma (COS) and metastatic lesions (C-SLM) were 18.4–19.1-fold elevated as com- pared to the value for abdominal muscle. The results suggest that activation of telomerase occurs in rat osteosarcomas but that it is not directly involved in determining their metastatic potential.  1997 Elsevier Science Ireland Ltd. Keywords: Telomerase; Telomere; Transplantable osteosarcoma; Rat 1. Introduction Telomerase is a ribonucleoprotein [1,2] which cat- alyzes the formation of telomere repeats present as TTAGGG at the end of chromosomes in vertebrates [3]. Cells with no telomerase activity have telomeres which become gradually shortened in successive gen- erations [4]. Such a decrease of telomere DNA is associated with cellular senescence and when a criti- cal point is reached after many cell divisions, this limits proliferation, except for cells which have acquired immortality by reactivating telomerase. Technological improvement in methods to monitor human and animal telomerase activity, with develop- ment of a highly sensitive polymerase chain reaction (PCR)-based assay, has allowed an increase to be demonstrated in preneoplastic and neoplastic lesions. It is now clear that telomerase activation does not normally occur in most human adult tissues, the exceptions including germ cells, lymphocytes, hema- topoietic progenitor cells and epidermis [5–8]. In rodents, elevated activity has been reported for mouse skin papillomas [9], hamster pancreatic carci- Cancer Letters 117 (1997) 67–71 0304-3835/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3835(97)00201-2 * Corresponding author. Tel.: +81 7442 23051; fax: +81 7442 57308.