Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology最新文献

In comparison to the known carcinogenic properties of Acetoxymethyl-Methyl-Nitrosamine (AMMN) after oral or intraperitoneal application the dimethylnitrosamine derivative was tested by subcutaneous, intravenous and intrarectal route in male Sprague-Dawley or Wistar rats. AMMN proved to be primarily a locally acting carcinogen. However, a second mode of action is indicated by systemic carcinogenic properties found after i.v. and s.c. applications. The lung and heart, and to a less extent the kidney and earduct were found as target organs of distant carcinogenic response.

DNA repair time-course was studied after injury by N-methyl-N-nitrosourea (MNU) in rat liver cells of animals of different ages and in fetuses using hydroxyurea (HU) as inhibitor of scheduled DNA synthesis. DNA repair was a rapid phenomenon, more so in young adults than in newborns, and was not detectable in fetuses. A correlation seems to exist among organ sensitivity to carcinogen, age of animal and DNA repair.

The oral acute LD50 of N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in a 10% aqueous solution of dimethylsulfoxide (DMSO) amounted to approximately 90 mg/kg. After single oral application of 50 mg/kg (group I), 75 mg/kg (group II) and 100 mg/kg (group III) of MNNG in a 10% aqueous solution of DMSO, generalized papillomatoses of the forestomach were found in all BD-VI rats after a test period of 500 days. Squamous cell carcinomas could be detected in 7/24 (21%) rats in group I, in 12/26 (46%) in group II and in 7/23 (30%) in group III). Benign adenomatous dysplasia of the glandular stomach was diagnosed in 2 rats (8%) of group I, in 1 animal (4%) of group II and in 12 rats (52%) of group III. Adenocarcinomas of the glandular stomach were induced in 1 animal (4%) of both group I and II and in 8 rats (35%) of group III. 20--30% of the animals treated with MNNG also showed degenerative cystic alterations in the liver with bile-duct proliferation.

Clear cell tumors of the salivary glands are monomorphic clear cell adenomas, clear cell carcinomas, clear cell variants of acinic cell and mucoepidermoid tumours, sebaceous cell tumors, salivary duct carcinomas and pleomorphic adenomas with clear cell sectors. At the light microscopical level the descriptive term of the clear cell comprises cell types of different origin and functional importance which can be differentiated by cytochemistry and electron microscopy. The following cell types were analysed precisely: indifferent duct cells (small formation of organelles, desmosomes), storing striated duct cells (glycogen granules, multiple mitochondrias, basal labyrinth), myoepithelial cells (myofilaments, pinocytosis vesicles, lipofuscin granules, hemidesmosomes), goblet cells (mucous vacuoles, basal endoplasmatic reticulum), sebaceous cells (lipid droplets, microvilli, desmosomes) and clear acinic cells (electron pale secretory granules, small mitochondrias, small golgi apparatus). Clear cell tumor types of the salivary gland region which primarely do not derive from the salivary gland tissue must also be included in the differential diagnoses. These are metastases of hypernephroid renal carcinomas, paragangliomas, glomus tumors of Masson, granular cell tumor and alveolar soft-part sarcomas.

Ultrastructural studies were done on cells from original tumors and from short time cultures of mouse thymic lymphomas experimentally induced by chronic exposure to diphenyl-hydantoin. The tumors appeared in mouse strains with low (C57Bl) and high (SJL/J) susceptibility to spontaneous lymphoma development and were not observed in a resistant strain (C3Hf). Thymic lymphoma development was usually preceded by increasing lymphoreticular atrophy followed by progressive reticulohistiocytic hyperplasia, and subsequently spread to other tissues. Morphologically the tumor was characterized as a lymphoblastic lymphoma. Abnormal cell changes in the original tumors and cultured cells, and the presence of murine C-type particles in the cultured cells but not in the original tumors, are discussed in relation with the disturbance of immune system and the lymphoma enhancement produced by diphenyl-hydantoin.

Chronic weekly oral and subcutaneous administration of N-Benzyl-N-nitrosourea induced carcinomas of the forestomach and local s.c. sarcomas respectively in BD-rats. This confirms a local carcinogenic effect of the compound. In prenatal experiments in BD-rats no carcinogenic effect of BzNH could be found.