Aortic rupture and aortic smooth muscle tumors in mice. Induction by p-hydrazinobenzoic acid hydrochloride of the cultivated mushroom Agaricus bisporus

Abstract

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.