Correlation of cocarcinogenic activity among n-alkanes with their physical effects on phospholipid micelles.
N-alkanes from C12 to C28 were tested for their cocarcinogenic or promoting activities to evaluate a correlation of their biologic activity with their effects on transport properties of phospholipid micelles. On this basis, we had predicted that the C18 and C20 homologues would be more active than the better known dodecane. The C12, C16, C18, and C20 n-alkanes, at various dilutions from 6 to 40% by volume in decahydronaphthalene (Decalin), were tested for their relative activity in a cocarcinogenic relationship to benzo[a]pyrene. At a 20% alkane concentration level, the solutions containing octadecane and eicosane induced tumors most rapidly. A 40% dodecane concentration was required to produce this level of cocarcinogenic activity. The activity of octadecane paralleled its physical effects on transport kinetics closely in the 6-40% (by volume) concentration. The C18, C20, and C28 n-alkanes and the C30 olefin squalene at dilutions from 10 to 40% in Decalin (by volume) were tested for their relative promoting activity after a single application of 7,12-dimethylbenz[a]anthracene in benzene. At comparable mole fractions in Decalin, the three n-alkanes had essentially the same promoting activity; squalene, at 20%, showed only borderline activity. Thus the high biologic activity of the C18, C20, and C28 n-alkanes correlated well with their physical effects on the structure of phospholipid micelles (chain-chain interactions of the alkanes with the acyl chains of the lipid). This correlation was interpreted as a strong indication that the liquid crystalline region of the phospholipid assembly (adjacent to the aqueous interface) in the membranes of latent (initiated) cancer cells was the site of action of hydrocarbon cocarcinogens. Application of a modified physical model to pristane, a branched-chain C19 alkane from coal and Colorado shale, indicated higher cocarcinogenic activity than that of n-C18H38. Applied to purified samples of docosane and tetracosane, activity comparable to that of octadecane was indicated.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D001580:Benzopyrenes; D008297:Male; D051379:Mice; D008823:Micelles; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010743:Phospholipids; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D000473:Alkanes; D001580:Benzopyrenes; D008823:Micelles; D010743:Phospholipids; D015127:9,10-Dimethyl-1,2-benzanthracene