Paul Kotin

INHIBITION OF CARCINOGENESIS. THE EFFECT OF HYDROCARBONS AND RELATED COMPOUNDS.

(1964). Inhibition of Carcinogenesis. Archives of Environmental Health: An International Journal: Vol. 9, No. 2, pp. 169-179.

Organic peroxides, hydrogen peroxide, epoxides, and neoplasia.

Preliminary data are reported that support the suspicion that organic peroxides may possess carcinogenic properties. This suspicion in large measure relates to the acknowledged mutagenicity of certain peroxides. As a possible mechanism of action it is suggested that peroxides may act by catalyzing the depolymerization of deoxyribonucleic (DNA) and ribonucleic acid (RNA). This radiomimetic property may provide a fundamental bridge between the carcinogenicity of ionizing radiation and that of organic peroxides when used in pure form. Emphasis has also been directed to the carcinogenic properties of epoxides. Organic peroxides may lead to the formation of epoxides, and the established carcinogenicity of epoxides has resulted in the accumulation of a large body of information relating to the mechanism of their action. Of particular significance in this area is their capability of acting as crosslinking agents. The possibility of utilizing the established carcinolytic properties of certain carcinogenic agents in the study of the carcinogenic properties of organic poroxides is discussed. (auth)

ATMOSPHERIC FACTORS IN PATHOGENESIS OF LUNG CANCER.

Publisher Summary This chapter focuses on the atmospheric factors in pathogenesis of lung cancer. The rise in lung cancer incidence is consistent with the introduction of new etiological influences into the respiratory environment around the start of the 20th century. Because lung cancer, in common with other neoplasms, appears unlikely to be the result of a single initiating or promoting experience, it is necessary to assess the pathogenetic significance of polluted air both for the detection of the presence of carcinogens and determination of its role with reference to that of other known or suspected environmental factors, for example, cigarette smoking and chronic pulmonary infection. Assessment of the significance of environmental factors, including polluted air, in the pathogenesis of lung cancer is partly dependent on analyses of the nature, rate, and temporal characteristics of the observed increase. Experimental considerations have been discussed in the chapter. Bioassay studies discussed in the chapter include painting and injection studies, and inhalation studies. The section on clinical lung cancer covers pathological aspects. Data from several spheres of laboratory investigation lend support to the belief that the epidemiological association between urban residence and lung cancer is of pathogenetic significance.

THE RESPONSE OF MUCUS-SECRETING EPITHELIUM AND MUCUS TO IRRITANTS*

The increased incidence of lung cancer has directed attention to the presence and sources of carcinogenic agents in the respiratory environment.lS2 Experimental and clinical studies suggest that a critical stage in the pathogenesis of lung cancer may be related to the state of physiological defenses of the respiratory t r a ~ t . ~ . ~ One of the functions of the mucous blanket covering the respiratory epithelium is the protection of the underlying cells against the adverse effect of inhaled materials. This is accomplished by the mechanical barrier provided and by the continuous cephalad flow of the mucous stream transporting particulates as well as liquid and gaseous substances to the oropharynx. The physiological rate of flow is sufficient to render unlikely the abnormal accumulation and prolonged residence of particulate chemical agents or viruses at any given site. We have been concerned with the effect of inhaled environmental agents on the secretion of mucus from the respiratory epithelium and on the activity of ciliated cells that provide the motive power for mucous flow. Experimental data indicate that attenuation of this physiological defense is uniquely compatible with facilitating the biological action of environmental carcinogenic agents and associated materials facilitating their effect. Carcinogens usually occur adsorbed on soot particles or as aerosols. Other substances or agents, although noncarcinogenic, may help modify host defenses so that the action of carcinogens may be facilitated. There are several bases for postulating alterations in the anatomy and physiology of the epithelium. These include the following. (1) The elution of carcinogenic hydrocarbons from soot requires a time interval and a certain milieu, both of which are met by the action of respiratory tract macrophages. (2) Accumulation of particles permits the local concentration of carcinogenic agents at particular sites. (3) Irritants are capable of producing superficial cellular necrosis with desquamation and accompanying denudation of the underlying basal layer of the epithelium. The irritant effect, although varying quantitatively, seems to be essentially nonspecific in that chemical, physical, and viral agents all seem capable of inducing the changes observed. In addition squamous metaplasia has been noted as a consequence of exposure to irritants and viral agents.lS6 The ubiquity of irritants, particularly in urban polluted air and cigarette smoke, two established sources of carcinogenic hydrocarbons, enhances the likelihood of combining biological action, either through simultaneous or sequential inhalation. * From the Department of Pathology of the University of Southern California School of Medicine and the Department of Pathology of the Los Angeles County General Hospital. This investigation was supported by a grant (RG3962) from the National Cancer Institute, Public Health Service, and a grant from the Scientific Advisory Board to the Tobacco Industry Research Committee.

Basic Science Aspects of Research in Environmental Health

(1968). Basic Science Aspects of Research in Environmental Health. Archives of Environmental Health: An International Journal: Vol. 16, No. 1, pp. 66-68.