The carinogenicity of N-hydroxy-N-2-fluorenyl-acetamide and the matabolism of N-2-fluorenyl-acetamide in Praomis (mastomys) natalensis

Abstract

ATTENTION to the mastomys [Rattus natalensis, Praomis natalensis (Davis, 1965;Snell and Stewart, 1967), multimammate mouse (Oettle, 1961)] as a useful species for investigations on the etiology of cancer was drawn first by the late Dr. Oettle (1955Oettle ( , 1957 who observed that older mastomys exhibited spontaneous gastric adenocarcinoma. These findings were confirmed by others, notably by Snell (1965). Additionally Oettle et al. (1959) noted that old animals infected with cercariae of Schistosoma mansoni had hepatoma.N-Hydroxy-N-2-fluorenylacetamide (N-OH-FAA) is an active metabolic intermediate derived from the well-known carcinogen N-2-fluorenylacetamide (2-acetamidofluorene, FAA). When fed to rats, in addition to the numerous tissues normally affected such as liver, mammary gland, ear duct, N-OH-FAA also gives neoplasms in the forestomach of rats (Miller et al., 1961). It seemed of interest, therefore, to examine whether the propensity of the mastomys towards carcinoma of the glandular stomach could be enhanced and this difficulty induced tumour obtained reliably and more quickly by feeding N-OH-FAA to this species. The present report deals with the results obtained. At the same time, the capability of mastomys to metabolise aromatic amine derivatives such as FAA to the active N-hydroxy derivatives was studied. MATERIALS AND METHODS Treatment of animalsWeanling male and female mastomys were obtained from the Animal Production Section of the National Institutes of Health. They were maintained in groups of 5 or singly in stainless steel screen-bottom hanging cages with free access to diet and water. In preliminary experiments it was found that mastomys refused to eat and did poorly on a semi-synthetic diet (see Shirasu et al., 1966) with or without carcinogen. Mastomys grew well on ground Purina laboratory chow. Toxicity tests determined that mastomys were more tolerant to N-OH-FAA than rats. Thus, definitive tests were set up at 2 dose levels, 0-06 per cent and 0 1 per cent of finely powdered N-OH-FAA, incorporated into ground Purina laboratory chow.A total of 72 male and female mastomys were divided into a control group and groups receiving 0 06 and 0 1 per cent N-OH-FAA. The animals were weighed