T H E POSSIBLE BIOLOGICAL SIGNIFICANCE OF
INTERACTIONS BETWEEN PQLYCYCLIC
HYDROCARBONS AND STEROLS
I N SURFACE FILMS1
G . H. A. CLOWES, W. W. DAVIS,
AND
M. E. KRAHL
(From the Lilly Research Laboratories, Indianapolis)
In a series of experiments previously reported ' measurements were made
of the interaction of polycyclic hydrocarbons with sterols in mixed surface
films on water. The data briefly presented here supplement those studies.
Altogether 3 1 hydrocarbons and three sterols, cholestanol, cholesterol, and
ergosterol have been studied.
Two types of interaction between a given hydrocarbon and a given sterol
are observed. The forces involved in each type, while not so great as those
holding individual atoms of single molecules together, appear to be sufficiently
great to be of biological significance.
In the interaction which we shall designate as Type I each hydrocarbon
molecule appears to be held in the mixed surface film between two sterol molecules so oriented that the methyl-free faces of the sterol molecules are in contact with the opposite faces of the hydrocarbon ring system. This interaction
tends, with a given hydrocarbon, to be strongest with cholestanol, less marked
with cholesterol, and weakest with ergosterol, as would be expected from the
decrease in perfection of packing as the sterol is varied in this order.
In the other type of interaction, Type 11, each hydrocarbon molecule appears to be held in two-dimensional solution in the sterol surface film. Type I1
interaction is less dependent on a high degree of orientation than Type I.
Although each of the 3 1 hydrocarbons so far studied has exhibited some
degree of Type I1 interaction with cholesterol or cholestanol, this type is
particularly marked with those hydrocarbons having aliphatic side chains attached to the polycyclic ring systems.
Evidence, derived in part from studies on cell membranes and in part from
surface film experiments, indicates that sterol molecules in vivo are arranged
with a relatively high degree of mutual orientation, perhaps face to face with
the hydroxyls of adjacent molecules in the same direction, perhaps face to face
with the hydroxyls of adjacent molecules in opposite directions. When hydrocarbon molecules are presented in vivo to such pairs of properly oriented sterol
molecules, their tendency to exhibit a Type I interaction will perhaps be at a
maximum with such substances as 3 :4-benzpyrene. Hydrocarbon molecules
may be transported from the site of administration to the site of action by
means of either Type I or Type I1 interaction, with the latter playing perhaps
the most important r6le in this respect and thus giving polycyclic hydrocarbons
with alkyl side chains a high transportability.
1 Abstract of paper delivered before the Third International Cancer Congress, Atlantic City,
Sept. 11, 1939.
%Am.J. Cancer 36: 98, 1939.
453
454
G. H . A. CLOWES, W. W. DAVIS AND M. E. KRAHL
If hydrocarbon-sterol interactions are significant for cancer production,
then a tentative explanation of the structural specificity in carcinogenicity of
hydrocarbons may be proposed in terms of these two factors. For example,
3:4-benzpyrene, an active carcinogen, has a relativeIy low ability to be transported but a high capacity for oriented interaction; 10-methyl-1:2-benzanthracene, also an active carcinogen, is transported readily and has a low but
significant tendency toward oriented interaction; 10-butyl-1:2-benzanthracene,
a non-carcinogen, is transported readily but has almost no capacity to ‘‘ fit ”
properly because of the strong tendency to Type I1 interaction imposed by
the butyl group; 20-methylcholanthrene, a very powerful carcinogen, has a
high capacity for oriented interaction and is also very readily transported.