7,12-Dimethylbenz(a)anthracene (DMBA) and the 7-hydroxy-, 7,12-dihydroxy-, and 4-methoxy- derivatives were studied in parallel to determine their effects on the hemopoietic system, adrenal cortex, liver enzymic activity, and body weight in Sprague-Dawley female rats. The monohydroxy compound caused more extensive damage to hemopoietic and adrenocortical tissue than DMBA, whereas the 7,12-dihydroxy- and 4-methoxy- derivatives were inactive. Liver menadione reductase and N-2-fluorenylacetamide hydroxylase activities were stimulated by DMBA and 4-methoxy-DMBA, but not significantly by the hydroxymethyl compounds. Mean body weight was not influenced by 4-methoxy-DMBA or 7,12-dihydroxy-DMBA. DMBA induced a temporary loss of body weight, whereas 7-hydroxy-DMBA caused a significant and prolonged loss. These observations strongly support the conclusion that DMBA-induced hemopoietic and adrenocortical damage is due to its metabolite, 7-hydroxy-DMBA.

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Supported by Grants No. CA07321 from the NIH, USPHS, and No. E-307 from the American Cancer Society.

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