Comparative Dosimetry of Radon in Mines and Homes (1991) / Chapter Skim
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Cells of Origin for Lung Cancer
Cells of Origin for Lung Cancer
Pages 166-193
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From page 166... ...
Thus, the committee reviewed evidence relevant to the question of whether all cells of the respiratory tract can be transformed to produce lung cancer or whether the risk is limited to a particular subpopulation such as the basal cells alone or basal cells and secretory cells. Also relevant is the location in terms of airway branching where the lung cancers originate, whether they arise exclusively from the cells in the central respiratory tract, whether they also can arise from cells of the lung periphery, or whether they can develop anywhere within the respiratory tract.
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From page 167... ...
Second, this conclusion is supported by observations that bronchial cells can be propagated in cell culture and can be malignantly transformed. These cell cultures, which are presumed to arise from the proliferative cells within the bronchi, can be transformed by gene transfection and can give rise to a spectrum of cancers that resemble the major varieties of lung cancers.
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From page 168... ...
The bronchial epithelium also contains basal cells and argentaffin neuroendocrine (Kulchitsky) cells.
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From page 169... ...
In fact, the vast majority of lung cancers are thought to develop from epithelial cells that line the
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From page 170... ...
Lung cancers are a class of tumors that have several typical morphological patterns based on light microscopic examination. The most common morphological types of lung cancers are squamous cell carcinoma, small cell undifferentiated carcinoma, adenocarcinoma, and large cell undifferentiated carcinoma.
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From page 171... ...
, often referred to as oat cell carcinoma, most commonly presents as a central tumor mass. Unlike other lung cancers, the bulk of the tumor is often found in the lymph nodes and connective tissue at the hilum of the lung.
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From page 172... ...
The tumor cells are typically very pleomorphic and have very prominent nucleoli. By light microscopy these tumors lack the cell bridging or nesting characteristic of squamous cell carcinomas and they lack keratin.
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From page 173... ...
The overall proportions of squamous cell carcinoma, small cell undifferentiated carcinoma, adenocarcinoma, and large cell undifferentiated carcinoma are, respectively, about 35, 17, 25, and 9% of all lung cancers in the male population of the United States. If one omits the other 14% of tumors in this study, the proportions become 41, 20, 29, and 10%, respectively, which are similar to the distributions of lung cancer types listed above.
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From page 174... ...
Therefore, cigarette smoking is an example of an environmental exposure that appears to shift the distribution of histological types of lung cancers. The information presented above largely concerns the characteristic of lung cancers as determined by light microscopy.
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From page 175... ...
This issue remains unresolved and requires further study, but one must entertain the possibility that small cell undifferentiated carcinomas may not originate from neuroendocrine cells of the respiratory tract. For example, other lung tumor cell types, particularly squamous cell carcinoma, are seen admixed with small cell carcinoma cells.
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From page 176... ...
It is also important to consider some past observations and some recent trends in lung cancer epidemiology, since these may influence the types of lung cancers that will emerge in the future and thus may be relevant to radon exposure (DHHS, 19893. Although cigarette smoking is recognized as the leading cause of lung cancer, it is clear that several other environmental factors can influence lung cancer incidence by additive or synergistic interactions.
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From page 177... ...
Compelling evidence in support of the concept that lung cancer development is a multistep process was derived from prospective cytologic studies in which the development of lung cancer in uranium miners was observed to occur over the course of several years (Saccomanno et al., 1964, 1965, 1974~. By studying the cytologies of repetitive sputum samples from uranium miners, cytologic changes were found to proceed through a sequence of progressive steps from squamous metaplasia through various degrees of dysplasia, in situ carcinoma, and invasive carcinoma.
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From page 178... ...
As such, it may function as a tumor suppressor gene for small cell carcinomas and perhaps other lung cancers. In other studies of small cell carcinomas, loss of heterozygosity was found at 3p, 13q, and 17p (Harbour et al., 1988~.
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From page 179... ...
(1989) examined non-small-cell lung cancers for evidence of consistent DNA sequence deletions.
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From page 180... ...
The first question is which cells in the human respiratory tract may be the progenitor cells from which lung cancers develop? Which cells are at risk for malignant transformation?
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From page 181... ...
It is presumed that the cells of the lung that are sensitive to radon-induced cancer are those that are not terminally differentiated but still have the capability for division and differentiation (Crawford-Brown, 1987~. In the normal central respiratory tract, cell proliferation occurs at a very low rate.
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From page 182... ...
This suggests two pathways for respiratory tract cell proliferation and cell renewal (Figure 8-44. Thus, not only basal cells but also secretory cells of the tracheobronchial epithelium can proliferate.
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From page 183... ...
Kreyberg and others thought that small cell carcinomas were undifferentiated squamous cell carcinomas (Dunnill, 1982~. Because of cytological similarities between bronchial carcinoids and small cell undifferentiated lung cancers, opinion has evolved to regard them as the benign and malignant ends of a spectrum of neuroendocrine lung tumors (Gould et al., 1978, 1983a,b)
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From page 184... ...
From this perspective, neurosecretory cells may not be the origin of small cell undifferentiated carcinomas. Lung cancers often have mixtures of histological patterns (McDowell et al., 1978; Cotran et al., 1989~.
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From page 185... ...
Bronchial basal cell hyperplasia and squamous metaplasia are typically antecedents to dysplastic proliferative lesions and occur in areas near bronchogenic cancers of various histologic types (Dunnill, 1982~. Squamous metaplasia, dysplasia, and carcinoma in situ of the bronchus are usually multifocal and commonly occur in the central bronchi prior to the appearance of lung cancers (Spencer, 1977~.
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From page 186... ...
Cancers observed in Schneeberg miners were identified as lymphosarcomas, but probably were small cell undifferentiated lung cancers. Tumors found later in autopsies of miners from the adjacent Joachimshal region had a preponderance of small cell undifferentiated carcinomas.
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From page 187... ...
Whereas small cell tumors constituted as much as 76% of lung cancers in this population in 1964, it had declined to 22% by the late 1970s. During this time the proportion of squamous cell carcinomas increased to make up the difference.
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From page 188... ...
The tumors that appeared after a longer latency were predominantly squamous cell tumors. As time has gone by, the proportions of the various types of lung cancers among uranium miners has come to resemble the distribution of lung cancers observed in the general population that largely reflect the consequences of cigarette smoking.
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From page 189... ...
Whereas peripheral lung adenocarcinomas and even small cell carcinomas may arise in the peripheral lung of rodents, these appear to be very uncommon in humans, presumably based on patterns of exposure and the cell populations in the human respiratory tract at that level. Since adenocarcinomas are, if anything, underrepresented among the lung cancers in uranium miners, it is likely that effects of radon on bronchial gland cells are minimal.
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From page 190... ...
1981. Tumors of the Lower Respiratory Tract.
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From page 191... ...
1990. The roles of cell proliferation and gene replication in neoplastic transformation.
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From page 192... ...
Histologic types of lung cancer among uranium miners. Cancer 27:515-523.
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From page 193... ...
1988. Relationship of radioactive radon daughters and cigarette smoking in the genesis of lung cancer in uranium miners.
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