This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
The study of various carcinogens has permitted us to recognize and relate to complex carcinogenic activity another energetic influence exerted by two or more double bonds when present in a parallel reciprocal position in cyclic molecules. This led us to the concept of "synjugated formations" with 2, 3, 4 or more such parallel double bonds.
In studying methylcholanthrene, one of the most potent of the known carcinogenic agents, the curve of its absorption in ultraviolet light was considered. This curve is shown in Figure 112. The place and form of the peaks could be interpreted in a peculiar way when conjugated double bond formations were considered. In the curve of methylcholanthrene, we could recognize portions that correspond to an inverse of the curves obtained from various conjugated polyenes. Furthermore, the curve obtained through the spectral analysis of methylcholanthrene can be considered to have high similarities to the inverse of the curve of a mixture of conjugated polyenes. Figure 113 shows the spectral analysis of conjugated cod liver oil fatty acids, while Fig. 114 shows the inverse curve of mixture of conjugated fatty acids of cod liver oil in which conjugated di-, tri-, tetra-, penta- and hexaenes are identified. Figure 115 shows the comparison between the curve of methylcholanthrene and the inverse of the peaks of the mixture.
We were thus led to consider the conceptual interpretation of these curves in terms of the special relationship that exists between double bonds in the same molecule. In the classical concept, two double bonds are considered conjugated if two of their carbons are joined by a single bond. In the zig zag representation of aliphatic molecules, the conjugated double bonds fulfill this condition. (Fig. 116a) Applying this relationship to cyclic molecules, what was considered to correspond to conjugation, according to this criterion, did not show properties similar to conjugated aliphatic members. (Fig. 116b) This made us consider, as the condition for the properties present in conjugated formations, another character: the reciprocal parallelism between double bonds present as they appear in the aliphatic molecule. Two or more double bonds in a cyclic molecule would thus realize a similar kind of energetic formation when parallel, and would do so independently of the number of the single bonds present in between. (Fig. 116c) For didactic purposes, we have applied the term "synjugated" to energetic formations resulting from parallel double bonds separated by more than one single bond.
Fig. 112. An interpretation of the spectral analyses of methylcholanthrene. Curve (a) shows the spectral analysis in ultra violet of methylcholanthrene.
Fig. 113. The curve shows the spectral analysis of the mixture of conjugated fatty acids with members having from 2 to 6 double bonds, as obtained by treating cod liver oil fatty acids with KOH.
Thus, in the methylcholanthrene molecule, there exist formations composed of two, three and four parallel double bonds (Fig. 117), which we call di-, tri-, and tetraenic synjugated formations. It is logical to assume that they are important in determining the energetic aspect of this molecule when the relationship of its spectral analysis to the curve corresponding to the inverse of conjugated di-, tri- and tetraenes can be recognized. From the point of view of its relationship to the plurality of factors determining the carcinogenicity of a substance, the presence of parallel double bonds, and the synjugated formations which they constitute, is interesting. Theoretically, each one of these synjugated formations would by itself represent a reactive possibility. Although qualitatively similar, they would show manifest quantitative differences. It must be noted that, while they are not present in all carcinogens, they are in most active, realizing di-, tri-, tetra- and even penta synjugated formations. According to the concept of plural activity in carcinogenesis, synjugation, while not indispensable for carcino genetic activity, would represent one of the factors that can make it possible.
Fig. 114. This curve is the inverse of the curve of Fig. 113.
Together with the condensation of the π electrons in the K regions and the presence of polar groups, the twin and synjugated formations would confer high plural activity upon the molecules of active carcinogens. An energetic spectrum of a carcinogen can be established in which these factors can be presented systematically.
Fig. 115. Direct comparison between the curve of the spectral analysis of methylcholanthrene and the inverse of the peaks characteristic for the different conjugated fatty acids as seen in Figs. 113 and 114.
Figure 118 shows a spectrum for 9:10 Dimethyl 1:2:7:8 Dibenz anthracene.
In the light of this analysis, it appears logical to conceive that the carcinogenicity of a chemical compound is a result of many factors, and that the great differences in carcinogenic properties of various agents is the result of differences in their energetic spectra. The differences are consequently qualitative as well as quantitative. From this viewpoint, it is possible that the great carcinogenic activity recognized for some substances would correspond to the presence in them at once of a great number of energetic factors.
The study of the correlation between the presence of various energetic centers and carcinogenesis has been facilitated by relating carcinogenic changes to levels of organization. Taking place at different levels, the induced processes can be seen to correspond to an entire series of manifestations which, while present also in invasive cancer, often can be recognized in cases in which an invasive cancer is not induced. Following this view, it can be expected that carcinogenesis is the summation of a whole series of actions induced in the organism, some exogenous and others endogenous.
Fig. 116. Conjugation and synjugation. In the aliphatic chain (a) the presence of single bonds between the double bonds induce the parallel position of double bonds. It is this parallelism, which through the reciprocal influence exerted, induces the energetic characteristics of the conjugated formations. In the benzene molecule (b) where the double bonds, although separated by single bonds, are not parallel, the lack of this parallelism explains the lack of the properties characteristic to the conjugated formation. The parallelism when present in cyclic molecules (c) realizes the "synjugated" formations.
Synjugation in 20-Methylcholanthrene
Fig. 117. The parallel position of the existing double bonds in methylcholanthrene corresponds to a bi-, tri-, and tetrasynjugation.
Two K Regions * * Two Twin Formations One Trisynjugated Bond Two Tetrasynjugated Bonds
9:10 Dimethyl 1:2:7:8 - Dibenzanthracene
Fig. 118. The energetic picture of 9:10 dimethyl. 1:2:7:8 dibenzanthracene, shows the presence of two K regions, two twin negative formations, one trisynjugated bond and two tetrasynjugated bonds.
Consideration of the plurality of the factors which intervene in chemical carcinogenesis and make it a complex process leads us to consider viruses in the etiology and pathogenesis of cancer in a similar light.