A review of perchloroethylene and rat mononuclear cell leukemia

Mononuclear cell leukemia (MNCL) is an extremely common spontaneous disease of ageing F344 rats accompanied by splenomegaly, anemia, thrombocytopenia, and leukemic infiltration (initially of the spleen, liver, and lung). Rare in other rat strains, incidence in F344 rats is variable, has been increasing, and can exceed 70% in controls. MNCL cells possess natural killer (NK) cell characteristics and apparently, the neoplastic cells derive from large granular lymphocytes (LGL), hence the alternative name of LGL leukemia. LGL leukemia is uncommon in man and occurs in two forms: T-LGL leukemia which has a chronic course, and the much rarer NK-LGL leukemia. In addition to cell type, the latter resembles F344 LGL leukemia being acute in course and involving more pronounced splenomegaly and thrombocytopenia. Chemically related increases in MNCL in F344 rats have not been associated with induction of human LGL leukemia. Carcinogenicity studies of perchloroethylene (PERC) in several rat strains have shown moderate, not clearly dose-related, increases in MNCL only in F344 rats (two studies). There was no consistent decrease in latency and the incidence in the PERC treated groups is within the overall control range. As a response in a rat strain highly predisposed to developing MNCL, these results are not considered predictive for human cancer risk.