Mutagenic and carcinogenic potency of extracts of diesel and related environmental emissions: Two-stage carcinogenesis in skin tumor sensitive mice (SENCAR)

Abstract

Skin tumors can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase), followed by repetitive treatment with a noncarcinogenic tumor promoter. There is a very good dose-response relationship between the induction of the number of papillomas per mouse at early times (10 to 20 weeks) by either tumor initiators and promoters and the final carcinoma incidence after a longer latency (20 to 50 weeks) in SENCAR mice. This system not only can be used to determine the tumor initiating and promoting activities of a compound but if the agent is given repeatedly by itself one can also determine if it is a complete carcinogen, i.e., if it has both tumor initiating and promoting activity. In addition, if the agent is given concurrently with a known complete carcinogen or a tumor initiator one can also determine if the agent has cocarcinogenic or cotumor initiating activity or even possibly anticarcinogenic activity. Likewise, if the agent is given concurrently with a known tumor promoter one can determine if the agent has copromoting or antipromoting activity. Using the SENCAR skin carcinogenesis system we have undertaken the determination of the skin carcinogenic, cocarcinogenic, tumor initiating and promoting activities of various diesel emission particle extracts as well as for comparative purposes, standards such as benzo( a)pyrene and 12-0-tetradecanoylphorbol-13-acetate and extracts of emissions from a gasoline engine, roofing tar, coke oven and cigarette smoke condensate. Most of the studies are still in progress but some preliminary data is available on the comparative tumor initiating activities of the various samples at 14 weeks. Caterpillar diesel and cigarette smoke condensate were essentially without activity, whereas the Mustang gasoline catalyst and Olds diesel gave extremely low values although they were slightly above background. Roofing tar, coke oven and Nissan Diesel all gave moderate activity at high doses (1 to 10 mg) but when compared to benzo( a)pyrene were relatively low values.