Primary Lung Tumors in Mice Following the Cutaneous Application of Coal Tar

Murphy, James B.; Sturm, Ernest

doi:10.1084/jem.42.5.693

Cited by 66 publications

(7 citation statements)

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“…The earliest chemical carcinogen bioassays were directed at determining the cancer causingpotential of a given chemical at a specific site, i.e. skin (Yamagiwa and Ichikawa, 1918) or lung (Murphy and Strum, 1925). It was soon recognized that chemicals administered at a given site could cause cancer at distant locations in the body, often in unsuspected locations.…”

Section: Discussionmentioning

confidence: 99%

Pathology Requirements for Two-year Rodent Studies II. Alternative Approaches

McConnell

1983

Toxicol Pathol

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The preceeding paper described the origin and evolution of the pathology portion of carcinogen bioassays conducted under the direction of the National Cancer Institute (NCi) and subsequently by the National Toxicology Program (NTP). Review of 277 studies conducted under the NCI/NTP protocol suggested that the present number of tissues/organ5 was in excess to what is needed to detect if a given chemical induces cancer in rats and/or mice. In addition, the ability of the previous protocol to detect and define non-neoplastic chemically related lesions may be inadequate. This paper describes alternative pathology protocols and proposes one that will answer the question of a given chemicals' carcinogenic potential while at the same time give superior information on nonneoplastic chemical related pathology. In addition this protocol will reduce the volume of histopathology required in most studies by over 50%.

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Section: Discussionmentioning

confidence: 99%

Pathology Requirements for Two-year Rodent Studies II. Alternative Approaches

McConnell

1983

Toxicol Pathol

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“…The seminal publication by Yamagiwa and Ichikawa in 1915 in which they demonstrated that tar and soot (hydrocarbons & aromatic hydrocarbons) produced cancer on the skin of rabbits and mice, providing the first experimental evidence to confirm the observation by Perceival Pott in 1775 1 , 8 . In 1925 Murphy and Sturm demonstrated skin-painting mice with polycyclic aromatic hydrocarbons led to systemic exposure with subsequent induction of lung tumors 9 . In 1935 Sasaki and Yoshida’s studies show that dietary administration of o-amidoazotoluene produced liver cancer in rats 10 .…”

Section: The Pre-genomic Eramentioning

confidence: 99%

The Role of the Toxicologic Pathologist in the Post-Genomic Era<sup>#</sup>

Maronpot

2013

J Toxicol Pathol

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An era can be defined as a period in time identified by distinctive character, events, or practices. We are now in the genomic era. The pre-genomic era: There was a pre-genomic era. It started many years ago with novel and seminal animal experiments, primarily directed at studying cancer. It is marked by the development of the two-year rodent cancer bioassay and the ultimate realization that alternative approaches and short-term animal models were needed to replace this resource-intensive and time-consuming method for predicting human health risk. Many alternatives approaches and short-term animal models were proposed and tried but, to date, none have completely replaced our dependence upon the two-year rodent bioassay. However, the alternative approaches and models themselves have made tangible contributions to basic research, clinical medicine and to our understanding of cancer and they remain useful tools to address hypothesis-driven research questions. The pre-genomic era was a time when toxicologic pathologists played a major role in drug development, evaluating the cancer bioassay and the associated dose-setting toxicity studies, and exploring the utility of proposed alternative animal models. It was a time when there was shortage of qualified toxicologic pathologists. The genomic era: We are in the genomic era. It is a time when the genetic underpinnings of normal biological and pathologic processes are being discovered and documented. It is a time for sequencing entire genomes and deliberately silencing relevant segments of the mouse genome to see what each segment controls and if that silencing leads to increased susceptibility to disease. What remains to be charted in this genomic era is the complex interaction of genes, gene segments, post-translational modifications of encoded proteins, and environmental factors that affect genomic expression. In this current genomic era, the toxicologic pathologist has had to make room for a growing population of molecular biologists. In this present era newly emerging DVM and MD scientists enter the work arena with a PhD in pathology often based on some aspect of molecular biology or molecular pathology research. In molecular biology, the almost daily technological advances require one’s complete dedication to remain at the cutting edge of the science. Similarly, the practice of toxicologic pathology, like other morphological disciplines, is based largely on experience and requires dedicated daily examination of pathology material to maintain a well-trained eye capable of distilling specific information from stained tissue slides - a dedicated effort that cannot be well done as an intermezzo between other tasks. It is a rare individual that has true expertise in both molecular biology and pathology. In this genomic era, the newly emerging DVM-PhD or MD-PhD pathologist enters a marketplace without many job opportunities in contrast to the pre-genomic era. Many face an identity crisis needing to decide to become a competent pathologist or, alternatively, to become a ...

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“…There is thus in the case of the prostate a reservoir of malignancy which is drawn upon in proportion to the thoroughness of the examination, and it is probable that the same is true of the lung. Passey and Holmes (1935) in an elaborate study for the years 1894-1928 of the numbers of intrathoracic neoplasms in relation to admissions to sixteen hospitals, found an increase in such tumours in five hospitals only of the sixteen, and these authors conclude that the reader "will find it difficult to make out a serious case for any appreciable increase in the incidence of intrathoracic neoplasia in the period 1894-1928... ". This may be so, but it is difficult to see why the recent great increase in certification of deaths from cancer of the lung (Graph 2) did not take effect upon more of the hospitals dealt with by Passey and Holmes, for one cannot suppose that the diagnoses in these institutions in, say, 1919, left no room for improvement.…”

Section: Possible Factors Which Might Cause An Increase In the Dementioning

confidence: 99%

“…The interpretation of such experiments, and still more the drawing of any inferences from them which shall apply to man, is rendered difficult by the facts that in mice lung tumours (1) occur in mice which have not been exposed to road dust (e.g. in seven out of ninety control mice in Argyll Campbell's experiment); (2) are largely controlled by genetic factors (Andervont, 1935); and (3) can be produced by simple application of tar to the skin (Murphy and Sturm, 1925) or in some strains by injection sub cutem of carcinogenic hydrocarbons (Andervont, 1935;Schabad, 1935) by which last method inhalation is excluded altogether.…”

Section: Tarring Of Roadsmentioning

confidence: 99%

A Study of the Incidence of Cancer of the Lung and Larynx

Kennaway

1936

J. Hyg.

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XIIISummaryThe death certificates for cancer of the lung and of the larynx in males from England and Wales for the years 1921–32 inclusive, numbering 18,280, have been investigated.Sources of error in statistical work on death certificates are discussed.Latterly autopsies have been made upon about 28 per cent, of cases of cancer of the lung, and 9 per cent, of cases of cancer of the larynx. The increase in the recorded cases of lung cancer is not nearly accounted for by the increase of data obtained by autopsy.The agricultural and coal-mining industries show a low incidence of cancer of the lung and of the larynx.The factors which lead to silicosis appear not to be very active in producing cancer of the lung or larynx, but in metal grinders the incidence of cancer of the lung is 2¼ times that in the general population. A group of open-air occupations, where there is exposure to the dust of roads, have rather high ratios for cancer of the lung and of the larynx with the exception that motor drivers have a normal liability to cancer of the larynx. On the whole, no occupation involving exposure to any kind of dust has been found in which there is any very high incidence of cancer of the lung or larynx. Cases of cancer of the lung in asbestos workers are described in recent literature, but none has been found among the certificates considered here (up to 1932).Workers exposed to coal gas and tar, and those engaged in the preparation and sale of tobacco, tend to show an increased prevalence of cancer of the lung.Occupations concerned with the supply of alcohol have a high incidence of cancer of the larynx.To investigate the occupational incidence of cancer thoroughly one should have before one, simultaneously, comparable figures for cancer of all parts of the body which could be effected by an external agent.With regard to the view, that the recent rapid increase in recorded deaths from cancer of the lung is due to the detection of more cases by improved diagnosis, the very moderate ratio (129) for cancer of the lung in medical men is noteworthy, for this is an occupation where the availability of the existing methods for the detection of cancer is presumably at a maximum.Data are given of the prevalence of cancer of the lung and larynx in men and in women, and of the rate of increase in the two sexes in recent years. The greater incidence of cancer of the lung upon men than upon women is discussed. The recent rate of increase of cancer of the lung in men is found to be not much greater than that in women, when these increases are reckoned in percentages.The increase in recorded cases of cancer of the lung may be due to (1) an actual increase; (2) improvement in diagnosis; (3) fashion in diagnosis; or to any combination of these factors. A comparison is made between the increase of cancer of the lung, and of cancer of the prostate; the number of deaths attributed to cancer of the prostate appears to have reached a steady level.No special occupations have been found to which the increase in the total of cases of cancer of the lung can be attributed; rural workers show an increase which is not much less than that in the general population.No evidence has been found that tarring of roads has affected the incidence of cancer of the lung upon the general population. Such data as are available suggest that coal tar in the atmosphere, whether derived from roads, domestic chimneys, or any other source, does not readily give rise to cancer of the lung. Cotton-mule spinners show an especially small liability to cancer of the lung although they inhale air sprayed with an oil which produces cancer of the skin.Improvements in diagnosis must have led to the detection of a larger proportion of the existing cases of cancer of the lung; whether there has been an actual increase in these cases cannot be decided from the data presented here, but a source of evidence on this question is suggested.We are indebted to the Registrar-General for the data considered in this paper, and also for kindly permitting us to use some figures which have not yet been officially made public. We have received much assistance in the classification of occupations from some members of the Staff of the General Register Office, to whom we wish to express our gratitude. We wish to thank also Dr J. C. Bridge, Senior Medical Inspector of Factories, for information upon various matters, and especially upon silicosis. We are greatly indebted to Miss L. D. Henderson for much assistance in carrying out the calculations.

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Primary Lung Tumors in Mice Following the Cutaneous Application of Coal Tar

Cited by 66 publications

References 1 publication

Pathology Requirements for Two-year Rodent Studies II. Alternative Approaches

Pathology Requirements for Two-year Rodent Studies II. Alternative Approaches

The Role of the Toxicologic Pathologist in the Post-Genomic Era<sup>#</sup>

A Study of the Incidence of Cancer of the Lung and Larynx

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