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Tumor Induction with the N'-Acetyl Derivative of 4-Hydroxymethylphenylhydrazine, a Metabolite of Agaritine of Agaricus bisporus¹

The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68105

N'-Acetyl-4-(hydroxymethyl)phenylhydrazine was administered as a 0.0625% solution in drinking water continuously for the life span of Swiss mice, from 6 weeks of age. Compared to that in untreated controls, in treated animals the lung tumor incidence rose from 15 to 34% in females and 22 to 48% in males, whereas the incidence of blood vessel tumors increased from 8 to 32% in females and from 5 to 30% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and angiomas and angiosarcomas of the blood vessels.

The commonly eaten mushroom Agaricus bisporus contains ß-N-[-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, which under certain conditions yields 4-hydroxymethylphenylhydrazine and L-glutamic acid. Since 4-hydroxymethylphenylhydrazine is relatively unstable, Its acetyl derivative was synthesized for this study. The possible environmental significance of the findings is discussed.

¹ This work was supported by USPHS Contract NO1 CP33278 from the National Cancer Institute, NIH. This study was presented in part at the 68th Annual Meeting of the American Association for Cancer Research, Denver, Colo., Mary 21, 1977 (17).

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