Cytological prognosis in cancer of the uterine cervix treated radiologically

Graham, Robert; Graham, John B.

doi:10.1002/1097-0142(1955)8:1<59::aid-cncr2820080107>3.0.co;2-q

Cited by 55 publications

(9 citation statements)

References 6 publications

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“…It follows that the cellular machinery can continue to function for fairly long periods before the existence of the latent defects is betrayed. In this connection, the common appearance of giant cells in the tissues of animals exposed to radiation (16) is most convincing evidence of the existence of a basic similarity in the processes which occur ilt dvo and those here found for cells in vitro.…”

Section: Discussionsupporting

confidence: 77%

Action of X-Rays on Mammalian Cells

Puck

Morkovin

Marcus

et al. 1957

The Journal of Experimental Medicine

251

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Survival curves of normal human cells from a variety of tissues exposed to varying doses of x-irradiation have been constructed, which permit definition of the intrinsic radiation sensitivity of the reproductive power of each cell type. The mean lethal dose of x-irradiation for all the cells employed, including those from normal and cancerous organs, those exhibiting diploid and polyploid chromosome number; those from embryonic and adult tissues, including recently isolated cells and cultures which had been maintained in vitro for many years, and cells exhibiting either epithelioid or fibroblastic morphology, was found to be contained between the limits of 50 to 150 r. Other similarities in the pattern of radiation effects, such as giant formation and abortive colonial growth, in these cells and that of the HeLa S3, previously studied, confirm the hypothesis that the pattern of reaction to x-irradiation previously elucidated, is representatative, at least in over-all outline, for a large variety of human cells. While the radiation survival curves of various human cells are similar in the gross, small but important characterizing differences have been found. All epithelioid cells so far studied are approximately 2-hit, and more radioresistant than the fibroblast-like cells whose survival data correspond to a mean lethal dose of around 60 r, and which so far can be fitted by either 1-hit or 2-hit curves. The earlier prediction that the major radiobiologic damage to mammalian cells is lodged in the genetic apparatus was confirmed by the demonstration of high frequency of mutants among the survivors of doses of 500 to 900 r. All the data on the x-radiosensitivity of these cells can be explained on the basis of a defect resulting from primary damage localized in one or more chromosomes. These considerations afford a convincing explanation of several aspects of the mammalian radiation syndrome.

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Section: Discussionsupporting

confidence: 77%

Action of X-Rays on Mammalian Cells

Puck

Morkovin

Marcus

et al. 1957

The Journal of Experimental Medicine

251

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“…Giant formation in mammalian cells has also been observed by Graham and associates (24) who have carefully studied the appearance of these forms in irradiated tumors, and have based an index of the tumor susceptibility on the per cent of giants appearing in smears after various x-ray doses. The present data are completely consistent with those of Graham and leave little doubt that the processes observed in vitro are close counterparts to those seen in the body.…”

Section: Discussionmentioning

confidence: 76%

Action of X-Rays on Mammalian Cells

Puck

Marcus

1956

The Journal of Experimental Medicine

1,527

456

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The effects of x-irradiation have been quantitatively studied on single cells of a human cervical carcinoma (HeLa) under conditions such that 100 per cent of the unirradiated cells reproduce in isolation to form macroscopic colonies. This technique eliminates complexities due to interactions of members of large cell populations. Survival of single cells (defined as the ability to form a macroscopic colony within 15 days) yields a typical 2 hit curve when plotted against x-ray dose. The initial shoulder extends to about 75 r, after which a linear logarithmic survival rate is obtained, in which the dose needed to reduce survivors to 37 per cent is 96 r. This radiation sensitivity is tens to hundreds of times greater than that of any microorganism for which the equivalent function bas been studied. Evidence, though not proof, is presented that the lethal effect is due to a radiation-induced genetic defect which, however, cannot be a simple single gene inactivation. The locus of the action could be chromosomal. Beginning at doses of 100 r, or possibly earlier, growth-delaying effects of radiation are visible. Cells in which the ability to reproduce has been destroyed by doses below 800 r, can still multiply several times. At higher doses even a single cell division is precluded. A large proportion of the cells killed by radiation at any dose gives rise to one or more giant cells. These metabolize actively, grow to huge proportions but never reproduce under the experimental conditions employed. Methods of preparing large populations of giant cells are described. These giants are particularly susceptible to virus action. Some of the irradiated cells disappear from the plate, presumably by disintegration. This action of radiation is by far the least efficient, since even after 10,000 r, 5 to 10 per cent of the original cell inoculum is recoverable as giants.

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“…(2) Special Investigations K. M. Graham and J. B. Graham (1947, 1955, 1960 in their laboratory studies on host response, maintain that prognosis can be related to the response of normal vaginal cells before and during radiotherapy. Three types of response are described :…”

Section: Host Response (1) Clinical Factorsmentioning

confidence: 99%