The influence of various polycyclic hydrocarbons on the growth rate of transplantable tumours

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Abstract
The test substances in 0.03-1.0% aq. colloidal soln., Na-dispersol or sesame oil were injected intraperit. into rats, either in small daily doses or in 1 or 2 large doses. At the end of the 14-34 days, treated and control animals were killed and degree of inhibition of tumour growth detd. The strongly carcinogenic compounds 1:2:5:6-dibenzanthracene, 3:4-benzpyrene. 5:6-cyclopentane-l :2-benzanthracene, Na-1: 2:5:6-dibenzan-thracene-9:10-endo-[alpha]-[beta]-succinate, 3:4:5:6-dibenzacridine, in doses totalling 8-100 mg., produced immediate and prolonged inhibition of growth of the tumours on which they were tested, Jensen sarcoma, Walker carcinoma, Rous sarcoma (fowl), 3:4-benzpyrene and l:2:5:6-dibenzanthracene produced tumours. The greatest inhibition was obtained after adm. of 50 mgm. of l:2:5:6-dibenzanthracene in 21 dys. on a Walker carcinoma, mean wt. of treated tumour/ mean wt. control being 0.09. Not all the compounds were tested on all the tumours, but where comparative data were available, 1:2:5:6-dibenzanthracene was more effective than 3:4-benzpyrene. The inhibitory power of chrysene and the 1:2-, 4-methyl-l:2-, 6-rnethyl-l :2-, 3-methyl-l :2-, and 7-methyl-1:2-benzanthracenes, with carcinogenicity varying from weak to nil, was less than that of the 1st group. Of the 2 oestrogenic substances tested, 9:10-dihydroxy-9:10-di-[eta]-propyl-9:10-dihydro-l:2:5:6-dibenzanthracene was inhibitory, l-keto-l:2:3:4-tetrahydrophenanthrene was without effect. Anthracene, phenanthrene, pyrene, 1:2-cyclopenteno-phenanthrene, fluoranthene, triphenylene, dodecahydro-1:2-benzanthracene, perylene, 1:9-benzanthrone, diphenylene oxide, all non-carcinogenic, were all non-inhibitory. The evanescent inhibition produced by the inj. of anti-rat precipitin was in no way comparable to the prolonged inhibition produced by certain polycyclic hydrocarbons, all carcinogenic substances. The retardation of tumour growth rate was thus correlated with carcinogenicity, and was a specific effect of certain compounds; but not a specific effect on the tumours, since the growth rate of the whole body was also inhibited by these same compounds. In many cases ovulation and spermatogenesis were suppressed, so that part of the general growth-inhibitory effect was attributable to interference with pituitary function. The continued exposure of normal cells to growth-inhibitory agents resulted apparently in the emergence of a new cell type variant with a permanently increased fission rate, which could in its turn be inhibited by suitable agents.