Authors: Michael Gronow.
This is an account of the author’s research investigations on the identification of the low molecular weight thiols (LMWT) present in a variety of eukaryote cells, particularly cancer cells. The work was carried out periodically over some 60 years in a number of university and private laboratories as, and when, resources permitted: as a result, this research can be roughly divided into 7 phases.
The first phase arose from initial research into ways to improve cancer treatment by radiation treatment. The second was involved with studies of the thiols present in isolated nuclei and nucleoli. The third consisted of attempts to develop new techniques to isolate and identify the various nuclear protein thiol containing moieties of a rat hepatoma tumour. The fourth phase involved the successful isolation of the nuclear nonhistone proteins which contain the bulk of the nuclear thiol material, leading to study nuclear thiol changes during rat liver carcinogenesis. The fifth phase consisted of the discovery and isolation of “hidden” low molecular weight thiols in isolated nuclei from rat tumours and other tissues. After a break of some 14 years, when bulk preparations of whole human cells became available, it became possible to continue work again on the low molecular weight thiols. Phase six consisted of studies on the thiols found in the ASF of various tumour cell lines using the new analytical technologies which were developing at that time. The seventh phase evolved into studies on human prostate cancer cell lines. Here a method was developed which clearly demonstrated that, among the low molecular weight thiols present in these cells, there was “an elephant in the room”. This new thiol moiety, constituting 56.4% of the total cell thiols, was found to be concealed within the protein matrices of the cell, held in place, not covalently but possibly by ionic and hydrophobic bonding; deemed to be a “Conthiol”. It does not contain any of the constituents of known cellular thiols and has proved difficult to analyse due to its reactive nature.
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