Relative sensitivities of nuclei and cytoplasm of Amoeba proteus to chemical carcinogens and mutagens

Chatburn, Graham Richard (1977) Relative sensitivities of nuclei and cytoplasm of Amoeba proteus to chemical carcinogens and mutagens. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

The Amoeba Proteus single cell model has been used as a system for toxicological investigations of six chemical carcinogens and mutagens - N-methyl-N-nitrosourea, dimethyl sulphate, methylmethane sulphonate, hydroxylamine, hydrazine and 2(achloroppropylamino) ethyl napthylene hydrochloride.One of the unique features of this system is the high toleranceof cells to nuclear transfer. This enables observations indicating the cell nucleus or cytoplasm as the main site of action of toxic chemicals. Parameters considered have included cell survival, delays to mitotic cell division and abnormal divisions and cell growth.The toxic effects of N-methyl-N-nitrosourea, a potent carcinogen, were shown to be predominantly directed at the cell nucleus. Cells in the DNA synthetic phase of the cell cycle were most sensitive and long mitotic division delays during which abnormal growth occurred were observed.2(achloropisopropylamino) ethyl napthylene hydrochloride, a carcinogen, was similarly toxic through its action on the cell nucleus when cells were exposed in the presence of mammalian liver enzyme fractions. In the absence of the enzyme preparation this chemical was toxic through its action on the cell cytoplasm.Division delays were significant but sot as great as with N-methylN-nitrosourea.Dimethyl sulphate and methylmethane sulphonate, both carcinogens, were toxic to both the cell nucleus and cytoplasm. The results also demonstrate that treated cells with damaged nuclei in a viable cell cytoplasm could be envisaged.The toxicity of hydrazine and hydroxylamine, carcinogenic and non-carcinogenic respectively, was directed to the cell cytoplasm. The only effects on nuclei were observed as slight delays to mitotic cell division and in the case of hydrazine abnormal growth and division. It is more difficult, from these results, to envisage cells with damaged nuclei in viable cytoplasms arising. The results demonstrate some chemical properties that may be related to carcinogenicity. The concept that arises involves persistent nuclear lesions in viable cells as the basis for carcinogenic transformation, at least for chemicals which are carcinogenic through their DNA damaging ability.

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