Abstract
NEWBORN rats have proved strikingly more susceptible than weanlings to the hepatotoxic action of a single dose of the hepatocarcinogen retrorsine, and also to senkirkine and hydroxysenkirkine (cyclic diesters of otonecine). It is usually accepted that substances which induce principally liver tumours require “activation” by liver microsomal enzymes before they become “proximal” (locally acting) carcinogens. Newborn rats, however, are deficient in enzymes which metabolize drugs, but they are very susceptible to hepatocarcinogens. My work has led me to suggest that the “activated” species of pyrrolizidine alkaloids, aflatoxins and certain other carcinogens are the respective epoxides formed on their chemically reactive double bonds. The microsomal enzymes present in older rats probably accelerate the conversion of the epoxides into less active forms.
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SCHOENTAL, R. Hepatotoxic Activity of Retrorsine, Senkirkine and Hydroxysenkirkine in Newborn Rats, and the Role of Epoxides in Carcinogenesis by Pyrrolizidine Alkaloids and Aflatoxins. Nature 227, 401–402 (1970). https://doi.org/10.1038/227401a0
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DOI: https://doi.org/10.1038/227401a0
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