p-Hydrazinobenzoic
acid (HBA), an ingredient of the cultivated mushroom Agaricus bisporus, was given in hydrochloride form at a dosage of 0.125% in
drinking water for life to randomly bred Swiss mice. Previous studies had demonstrated that either synthetic or naturally occurring
hydrazines are carcinogenic in mice with the main
tumors so-induced being peripheral angiomas and
angiosarcomas. As a result of HBA treatment in the present experiments, smooth muscle cell
tumors of the aorta and large arteries were induced in 14% of females and 42% of males, whereas the corresponding frequency of
tumors in untreated female and male controls was 0 and 4%, respectively.
Tumors were observed as early as
at 17 weeks of age. Numerous experimental animals (32% of females and 50% of males) died of
aortic rupture. Histopathologically, two major changes were observed to explain both the
ruptures and
tumors. First, the intimal and inner medial aspect of the aortic walls had undergone effacement with widespread fibrinoid
necrosis, accompanied by medial elastinolysis. Second, a proliferation of cells arising in the media, benign in some aortae and frankly malignant in others, was strikingly positive by immunohistochemistry for cytoplasmic actin and
myosin, moderately positive for
desmin, weakly positive for
vimentin, and negative for
factor VIII-related antigen. When malignant, the
tumors extended into the periaortic adventitial connective tissue. The
tumors were classifiable as
leiomyomas and
leiomyosarcomas. Thus, HBA is an additional carcinogenic ingredient of the widely consumed mushroom, A. bisporus. A continuum from toxic tissue injury to cellular
hyperplasia, dysplasia, and ultimate
neoplasia is well-illustrated by HBA.