Promoting effect of polychlorinated biphenyls on development of enzyme-altered islands in livers of weanling and adult rats.

The promoting activity of the commercial PCB mixture Clophen A 50 on preneoplastic, enzyme-altered islands in rat liver was investigated. Female Sprague-Dawley rats, 3 and 6 weeks old, were pretreated with nitrosamines for island initiation. Thereafter Clophen A 50 was administered repeatedly. Island development was examined between 2 and 12 weeks. Clophen A 50 by itself initiated few enzyme-altered islands, indicating a weak carcinogenicity. In Clophen A 50-treated adult rats, the majority of nitrosamine-initiated islands persisted. Without Clophen A 50 more than 80% of the islands disappeared between 6 and 12 weeks. Moreover, PCBs caused a striking increase in island number and total area during the last 2 weeks. In weanlings, islands persisted with or without the promoting stimulus. However, treatment with Clophen A 50 caused an earlier appearance and a higher number and total area of islands. The increase in the yield of DEN-initiated islands in both age groups is suggested to be due to the promotion of initiated but dormant cells. By pretreatment with N-NM instead of DEN, a shift to larger islands was observed additionally. The data indicate that weanlings are highly susceptible to initiation and promotion and may thus provide a sensitive tool to screen for tumor initiating and promoting agents.