Differential Modification of Development of Preneoplastic Lesions in the Syrian Golden Hamster Initiated With a Single Dose of 2,2′-Dioxo-<italic>N</italic>-nitrosodipropylamine: Influence of Subsequent Butylated Hydroxyanisole, α-Tocopherol, or Carbazole<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

Abstract

The effects of butylated hydroxyanisole [(BHA) CAS: 25013-16-5], alpha-tocopherol [(TC) CAS: 59-02-9], and carbazole [(CA) CAS: 86-74-8] administered subsequent to a single dose of 2,2'-dioxo-N-nitrosodipropylamine [(DOPN) CAS: 60599-38-4] on the development of putative preneoplastic lesions were investigated in Syrian golden hamsters. Whereas the 2 antioxidants BHA and TC inhibited the incidence of both liver and pancreatic lesions, CA, itself giving rise to considerable numbers of enzyme-altered foci, enhanced carcinogenesis in the liver while inhibiting carcinogenesis in the pancreas. All 3 of these agents induced hyperplastic and papillomatous lesions in the forestomachs of treated animals, independent of prior DOPN treatment; these forestomach lesions were not evident in controls. Cellular atypia and invasive growth characteristics signifying malignant change were also observed in BHA-induced forestomach lesions. The results demonstrate that hepatocarcinogenesis in the Syrian golden hamster, like that in the rat, can be inhibited by antioxidants. The similar decrease in putative preneoplastic lesion yield evident in the pancreas of BHA- or TC-treated hamsters, considered in the light of similarities in altered enzyme phenotype in carcinogen-induced lesions of both organs, suggests that common biochemical changes can be an underlying factor in the modification of neoplastic development in liver and pancreas. The present results also provide further evidence that CA has carcinogenic potential for the liver and forestomach of experimental animals.