The Pathogenesis of Deferred Cancer

Abstract

The malignant tumors which arise in man on the basis of tissue injury sustained many years previously raise questions of prime moment for an understanding of how cancers come about. Have neoplastic cells, brought into being by the tissue disturbance, lain latent throughout all the tong interval? Or did the disturbance provide a carcinogenic stimulation insufficient in itself to convert normal cells into tumor cells but succeeded by others with result in such conversion eventually? Or can it have started a process gradually, yet inevitably, consummated in the course of time? There are facts in the clinical literature for each one of these assumptions. The present paper reports experimental findings which bear upon the course of events. The ears of young adult rabbits were painted with a solution of methylcholanthrene until a few benign growths had appeared, and then the paintings were stopped and the later cutaneous happenings,--which included the ultimate appearance of cancers,--were followed throughout the animals' lives. Pieces of the ears were punched out from time to time to learn the general state of the skin and to determine the character of equivocal growths, but more especially to test whether hidden neoplastic potentialities existed in the cutaneous tissue. For where punch holes are healing in ears previously treated with chemical carcinogens epidermal tumors frequently arise which would not have asserted themselves in the absence of stimulation (1). Material and MethodsFive young adult agouti rabbits of about 2.5 kilos weight were studied. The hairless side of their ears was swabbed all over twice weekly with a 0.3 per cent solution of methylcholanthrene (MC as it will be termed) throughout periods of from 215 to 250 days. Two of the animals (D. R. 1-69 and 1-72) received the hydrocarbon dissolved in benzene, and the other three (D. R. 3-37, 3-44, 3-45) in Crabtree's medium (2),--ethyl ether containing 2 per cent of light mineral oil (u. s. P. ingredients). The total period of observation ranged from 980 to *

Cell–cell contact interactions conditionally determine suppression and selection of the neoplastic phenotype

“…It supports the idea of regional neoplasia in which large areas of a tissue exposed to carcinogen are involved in the neoplastic process although the tumors arise locally (67). The process is strikingly exemplified after repeated paintings of rabbit ears with carcinogen, whereupon papillomas appear and disappear, with new ones continuing to appear for years after the paintings have ceased (68).…”

Are Carcinogens Responsible for the Superimposed Neoplastic Changes Occurring in Mouse Tumor Cells?

“…If the tumor cells of the present work failed in this transmission, their difference from normal cells was profound. These latter often continue to multiply for months or years after exposure to a carcinogen has ceased, doing so because of the chronic inflammation it has induced in the supporting tissue, and nevertheless tumors ultimately arise (13).…”

Trauma und Karzinom

“…Friedewald u n d Rous (1950) zeigten, daß die T u m o rla te n z von K an in ch en o h ren n a c h u n tersch w elliger M eth y lcholanthren-A nw end u n g a u f L eb en szeit b esteh en blieb, d. h. d u rch S ta n z u n g jed erzeit n ach w eisb ar w u rd e , a b e r w ohl n ic h t infolge A nw esenheit von la te n te n T um orzellen, so n d ern v on Zellen m it la te n te n n eo p lastisch en P oten zen v ersch ied en er A u sp rä g u n g : den neoplastischen Z u sta n d fortw äh ren d erreichen u n d an sch ließ en d in P ro liferatio n ü b erg eh en sollten Zellen o d er A bköm m linge v o n Zellen « t h a t had been no m ore th a n sta rte d on th e w ay to w a rd becom ing n eo p lastic by th e carcinogen». Also n ic h ts m eh r von einem im m e d ia te n In itia lv o rg a n g beim K o n ta k t m it dem K arzin o g en !…”