Neoplasia and chronic disease associated with the prolonged administration of dehydroheliotridine to rats

When dehydroheliotridine (DHH), a pyrrolizidine alkaloid metabolite with bifunctional alkylating and antimitotic activities, was administered to a hooded strain of rats by ip injection, the incidence of tumors, excluding interstitial cell tumors, was significantly greater than that in saline-injected controls. The number of tumors was not further increased when thioacetamide (TA) was co-administered for its mitosis-stimulating effect. The life-span of the rats was significantly shortened by DHH and more so by combined DHH and TA treatment, but not by TA alone. The results indicate that DHH is responsible for some, possibly most, of the carcinogenicity of the parent pyrrolizidine alkaloids and also stimulates the earlier and more rapid development of renal and vascular diseases normally associated with aging in rats.