Chapter 3, Note 1. Precancerous Lesions

Precancerous lesions were identified especially in cases in which cancerous lesions were induced and where a manifest polycentricity of lesions was present. (203) Polycentric lesions permit us to study the entire successive changes from normal to invasive cancer.

Induction of cancer in the stomach of rats through carcinogens and detergents (204) has furnished excellent material for such study; it has also permitted us to characterize the specific changes. Among cells which appear grossly normal, there are some in which certain morphological characteristics of the nucleus, notably size and form, appear abnormal. The existence of an anomaly is much more evident when the cell divides. It may be limited to just a few chromosomes which are abnormal in their dimension and form. This chromosomial abnormality appears still more evident when compared to cells in mitosis in controls with normal mucous membranes. (309)

Chapter 3, Note 2. Non Invasive Cancer

We have emphasized the character of the cytoplasm of the cells in non invasive cancer. The nuclei show a number of changes which, together rather than separately characterize a cancerous entity: an irregular shape of the nucleus with a manifest increase in size; a sharp nuclear border formed by a dark pigmented nuclear membrane having fine chromatine particles; a hyperchromatism with clumps of chromatin separated in bizarre, irregular fashion; and an uneven, irregular distribution of these chromatin clumps, concentrated near the nuclear membrane. Also often encountered is the presence of one or more irregular enlarged nucleoli, with a distinct nucleolar border and especially with a manifest acidophilic staining.

In the non invasive cancer, all these nuclear anomalies contrast with the relatively normal cytoplasm, which has not only an acidophilic reaction ócolored in orange with Papanicolau's trichromic stainingóbut also a well defined cell membrane with fairly clear cell border. The size of the cytoplasmócompared to other cellsóis normal, although the nuclear cytoplasmic ratio is increased due to the big nucleus. Due to the character of the cytoplasm, these cells were called the "third type differentiated cells" by Graham. (205) We emphasized the "normal" aspect of the cytoplasm of these non invasive cells, in contrast to the invasive cells where the abnormality includes both the nucleus and the cytoplasm. This explains why most of the invasive cells have little cytoplasm, an indistinct cellular border and a basophil cytoplasmic staining. (206) But besides these cells with totally abnormal cytoplasm, there are some invasive cells with an apparently differentiated cytoplasm. Although their staining is orthochromatic, their cytoplasm shows marked abnormality in form. The tadpole cells found in the exfoliative cytology in epidermoid carcinoma, (207) or the fiber cells (208) with abnormally long fibrillar cytoplasm revealed in other forms of invasive cancer indicate a participation of the cytoplasm in the abnormality. The cells found in so called "Bukhead's disease" with minimal abnormal cytoplasm thus appears to be at the boundary between non invasive and invasive cancerous cells.

Chapter 3, Note 3. Abnormal Amino Acids

We have seen above how the concept of hierarchic organization brought us to consider the alkaline amino acids and the histones which they form as one of the first members of the biological realm. Anomalies can be conceived to result from a process of resonance which occurs constantly on a statistical basis. As work hypothesis, we consider such resonance entities as corresponding to these abnormal forms, which in hierarchic development would lead to cancerous entities.

The naturally existing levorotatory alkaline amino acids represent the constituents which, through their number and role in further organization, represent normal entities. Opposed to them, the dextrorotatory alkaline amino acids would represent abnormal entities. Their existence and their role has made the object of many discussions without, however, bringing sufficient light to this problem. The constant existence in the body of specific enzymes against these dextrorotatory amino acids in spite of the fact that they are not recognizable analytically, indicates a certain defense against them. The concept of their appearance as a resonance phenomenon would explain easily this occurrence. Dextrorotatory amino acids, although abnormal for the organism, exist in practically all individuals as a resonance form, but they are not able to developóor develop in extremely reduced formóbecause of the enzymes which attack them. They are, however, able to develop the lowest levels of cancerous entities as they are recognized to exist practically in all normal individuals particularly after a certain age. There are these considerations which lead us to believe that it is the dextrorotatory resonance form of alkaline amino acids which represent the abnormal entities at the lower levels.