EARLY DEVELOPMENT OF INJECTION-SITE SARCOMAS IN RATS - A STUDY OF TUMOURS INDUCED BY A RUBBER ADDITIVE

A rubber additive polymerised N-nitroso-2,2,4-trimethyl-1,2-dihydroquinoline (NTDQ) was administered for 20 weeks by the subcutaneous, intraperitoneal and oral routes to 120 young Sprague-Dawley rats. Local sarcomatous changes were induced in rats injected subcutaneously and (to a lesser extent) intraperitoneally; feeding of large doses of NTDQ was ineffective. Some of the sarcomas which developed at injection sites were small lesions, only recognised at autopsy; in many animals, sarcomatous changes were not apparent until histological examination. These early sarcomatous lesions were studied in detail and three stages of development have been tentatively defined. (1) Tiny foci of abnormal fibroblasts, associated with increased amounts of acid mucopolysaccharide ground substance, form between the pre-existing masses of multinucleate giant cells which are seen at sites of injection of NTDQ. (2) These foci of abnormal fibroblasts enlarge and form circumscribed nodules, sharply demarcated from the surrounding tissues. (3) Some of these nodules become irregular in outline, invade adjacent tissues, and are recognisable as macroscopic neoplasms. Some of the changes evoked by NTDQ are reminiscent of the early neoplastic reactions associated with more powerful carcinogens such as the polycyclic hydrocarbons, macromolecular iron complexes, and certain plastics. The advantages of using a weak carcinogen such as NTDQ to trace the early development of induced sarcomata are discussed and some general implications of the present findings with regard to the interpretation of carcinogenicity testing are considered. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.