Starting from the theory that the carcinogenic polycyclic hydrocarbons are bound in the cell as inclusion compounds in protein molecules, some restrictivc steric factors are discussed:
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The relative carcinogenic indexes of the polycyclic hydrocarbons show selective distribution when plotted against the respective incumbrance areas (surface of the minimum rectangular envelope). The selectivity of the curve delimiting the ensemble of these points gives a stereochemical explanation for the change in activity by methylsubstitution.
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The carcinogenic activity of the polycyclic hydrocarbons does not vary appreciably by hydrogenation, unless the molecular thickness of the so obtained compounds does not exceed about 6 A . This corresponds approximately to the space between two protein layers, linked together by a cystine bridge.-The relative activities of the higher alkylsubstituted hydrocarbons and of the three natural oestrogenic hormones can he explained in this outline.
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The limiting effect of the molecular size on the carcinogenic activity shows up not only by steric hindrance but also by influencing the adsorbability of the hydrocarbons by secondary valence forces. Thus it was found that the ratio: sum of free valence indexes/molecular area decreases for large molecules.
The observable carcinogenic activity is interpreted as a result of the competition between the causative forces (interactions with a protein site) and the restrictive factors (steric hindrance, solubility, etc.).
- A steric model of the chemical carcinogenesis was elaborated. Co-carcinogenesis and anti-carcinogenesis are interpreted as promotion and hindrance of the entry of the polycyclic molecule inside a three-dimensional protein network.-A relationship is suggested between the promoting effect of X-rays on refractory animals and the molecular incumbrance area of the used carcinogenic hydrocarbons
The irreversible change in the cell, during chemical carcinogenesis, is interpreted as a definite configurational change in the protein network of a key enzyme or enzyme system, due to the weak ~denaturinya action of these compounds.