Carcinogenicity of some pyrrolic pyrrolizidine alkaloid metabolites and analogues.
Repeated topical doses of dehydromonocrotaline, a putative primary toxic metabolite of the pyrrolizidine alkaloid monocrotaline, followed by repeated treatments with croton oil, produced malignant tumours of the skin in LACA mice. A chemically similar alkylating agent, 2,3-bistrimethylace-toxymethyl-1-methylpyrrole, was carcinogenic without use of a promoter, confirming a preliminary report. Its high activity was due to the intact ester, not to its hydrolysis products. Dehydroretronecine (DHR), a less reactive secondary metabolite of monocrotaline, was also carcinogenic to LACA mouse skin, but it was less active than previously reported in experiments with another strain. Similar carcinogenicity was shown by the synthetic 2,3-bishydroxymethyl-1-methylpyrrole, but not by 2,3-bis-hydroxymethyl-5-methyl-1-phenylpyrrole, which has a high level of antimitotic activity.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003436:Croton Oil / Q000494:pharmacology; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D016686:Monocrotaline / Q000031:analogs & derivatives; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010421:Pentanoic Acids / Q000494:pharmacology; D011759:Pyrrolidines / Q000378:metabolism* / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced*
D000470:Alkaloids; D010421:Pentanoic Acids; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D003436:Croton Oil; C005566:pivalic acid