Examination of colon carcinogenesis and cocarcinogenesis induced by 1,2-dimethyl-hydrazine (DMH)

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1318 Abstracts EXAMINATIONOF COLON CARCINOGENESIS AND COCARCINOGENESIS INDUCED BY 1,2-DIMETHYL- HYDRAZINE (DMH). J.Sugar, O.Csuka and Z.Szentirmay. Research Instituteof Onco- pathology,Budapest,Hungary. Colon carcinogenesis inducedby DMH in Swiss and C57Bl mice has been investigated. The effect of phorbol ester TPA and Vincristin (VCR) on the outcome of DMH induced carcinogenesis has been studied. TPA treatmentincreasedthe number of hyperplastic foci in DMH treated animals, enhancedmetastasisformationand increasedthe incidence of squamouscell metaplasia in the stomach. VCR treatmentincreasedthe occurrence of perianal lesions inducedby DMH in Swiss mice. By computerized.cytophotometric analysisheteroploidDNA populationcould be detected in hyperplasiainduced by DMH or TPA. In carcinomasthe percentageof hyperdiploidcell populationis further increasedand 3 subpopulationacould be revealed. The DNA heteroploidyrefers to the genetic instabilityof the cells. TEM AND SEM STUDIES OF HUMAN BLADDER CARCINOMACELLS INVADINGEMBRYONICCHICK HEART FRAGMENTSIN VITRO. B.Szende,J.Kieler,K.Lapis and B.Christensen. Instituteof Pathologyand ExperimentalCancer Research, Sennnelweis Medical University,Budapest, Hungary and The Fibiger Laboratory,Copenhagen, Denmark, The Hu 961 cell line was establishedin vitro from a T-l (TNM-classification) transitional cell carcinoma (TCC) of the bladder from a 65 year old man. Histologically the tumourwas classifiedas a non-invasive, grade 2 tumour. The Hu 961 cell line is tumourigenic in nude mice, and in co-cultures with fragmentsof embryonicchick hearts, aggregatesof the Hu 961 cells invade and destroy the heart tissue. In the presentwork these cells and co-cultures were studied by transmission(TEM) and scanning (SEM) electronmicroscopy. The epithelialcharacterof the Hu 961 cells was verified in monolayer cultures as well as in co-cultures with heart fragments,and destruction of neighbouring muscle cells was demonstrated. EFFECTS OF Na-2-MERCAPTOETHANESULPHONATE (Mesna)ON THE CARCINOGENICITY AND MUTA- GENICITYOF N-NITROSO-n-BUTYL-N-(4-HYDROXYBUTYL)AMINE. A.M.Tacchi,D.Schm&l and B.L.Pool. Instituteof Toxicologyand Chemotherapy, German Cancer Research Centre, Heidelberg,F.R.G. There is evidence that Mesna inhibitsbladder carcinogenesis inducedbv cvclophosnh- amide (Habs et al., Cancer 51, 606-609, 1983). We invesiigated whether M&s& acts _ specifically against cvclophosphamide or exhibits a general protectiontowards _ - _ - _ chemically-induced bladder cancer. The bladder carcinogenNlnitroso-n-butyl-N- (4-hydroxybutyl)amine (BBNOH)was administeredto male Sprague-Dawley rats over a period of 9 months (5 g/kg by gavage) togetherwith Mesna(63 g/kg in drinkingwater). Control rats were given carcinogenalone and both groups were observed for life. Although Mesna did not reduce the tumour incidence,it significantly increasedthe life-spanof treated animals. Thus, at the dose levels used here, Mesna would appear to exert a partial detoxifyingaction against BBNOH. Mesna did not reduce the mutagenicityof BBNOH when tested in the histidine auxotrophSalmonellatyphimuriumTA 35.

Transcript of Examination of colon carcinogenesis and cocarcinogenesis induced by 1,2-dimethyl-hydrazine (DMH)

Page 1: Examination of colon carcinogenesis and cocarcinogenesis induced by 1,2-dimethyl-hydrazine (DMH)

1318 Abstracts

EXAMINATION OF COLON CARCINOGENESIS AND COCARCINOGENESIS INDUCED BY 1,2-DIMETHYL- HYDRAZINE (DMH). J.Sugar, O.Csuka and Z.Szentirmay. Research Institute of Onco- pathology, Budapest, Hungary.

Colon carcinogenesis induced by DMH in Swiss and C57Bl mice has been investigated. The effect of phorbol ester TPA and Vincristin (VCR) on the outcome of DMH induced carcinogenesis has been studied. TPA treatment increased the number of hyperplastic foci in DMH treated animals, enhanced metastasis formation and increased the incidence of squamous cell metaplasia in the stomach. VCR treatment increased the occurrence of perianal lesions induced by DMH in Swiss mice. By computerized.cytophotometric analysis heteroploid DNA population could be detected in hyperplasia induced by DMH or TPA. In carcinomas the percentage of hyperdiploid cell population is further increased and 3 subpopulationacould be revealed. The DNA heteroploidy refers to the genetic instability of the cells.

TEM AND SEM STUDIES OF HUMAN BLADDER CARCINOMA CELLS INVADING EMBRYONIC CHICK HEART FRAGMENTS IN VITRO. B.Szende, J.Kieler, K.Lapis and B.Christensen. Institute of Pathology and Experimental Cancer Research, Sennnelweis Medical University, Budapest, Hungary and The Fibiger Laboratory, Copenhagen, Denmark,

The Hu 961 cell line was established in vitro from a T-l (TNM-classification) transitional cell carcinoma (TCC) of the bladder from a 65 year old man. Histologically the tumour was classified as a non-invasive, grade 2 tumour. The Hu 961 cell line is tumourigenic in nude mice, and in co-cultures with fragments of embryonic chick hearts, aggregates of the Hu 961 cells invade and destroy the heart tissue. In the present work these cells and co-cultures were studied by transmission (TEM) and scanning (SEM) electron microscopy. The epithelial character of the Hu 961 cells was verified in monolayer cultures as well as in co-cultures with heart fragments, and destruction of neighbouring muscle cells was demonstrated.

EFFECTS OF Na-2-MERCAPTOETHANESULPHONATE (Mesna) ON THE CARCINOGENICITY AND MUTA- GENICITY OF N-NITROSO-n-BUTYL-N-(4-HYDROXYBUTYL)AMINE. A.M.Tacchi, D.Schm&l and B.L.Pool. Institute of Toxicology and Chemotherapy, German Cancer Research Centre, Heidelberg, F.R.G.

There is evidence that Mesna inhibits bladder carcinogenesis induced bv cvclophosnh- amide (Habs et al., Cancer 51, 606-609, 1983). We invesiigated whether M&s& acts _ specifically against cvclophosphamide or exhibits a general protection towards _ - _ - _ chemically-induced bladder cancer. The bladder carcinogen Nlnitroso-n-butyl-N- (4-hydroxybutyl)amine (BBNOH) was administered to male Sprague-Dawley rats over a period of 9 months (5 g/kg by gavage) together with Mesna(63 g/kg in drinking water). Control rats were given carcinogen alone and both groups were observed for life. Although Mesna did not reduce the tumour incidence, it significantly increased the life-span of treated animals. Thus, at the dose levels used here, Mesna would appear to exert a partial detoxifying action against BBNOH.

Mesna did not reduce the mutagenicity of BBNOH when tested in the histidine auxotroph Salmonella typhimurium TA 35.