Lung cancer Subject

The replacement of asbestos fibers by other fibrous materials has raised similar health issues in relation to substitute materials. However, since lung cancer has a latency period of approximately 25 years, and since the fiber exposure levels in contemporary industries is far lower than those which prevailed half a century ago, the epidemiological data on most substitutes is insufficient. A possible exception is slag fibers for which several studies on worker populations are available over extended periods (44) some results show a substantial increase in lung cancer occurrence. Consequentiy, the toxicity of asbestos substitute fibers remains a subject of active investigation. 

A somewhat related situation can be used to explain the well-publicized lung-cancer inducing effects of P-carotene in heavy smokers. This subpopulation will have low vitamin C levels and hence damage due to smoke components, such as N02 can produce P-CAR which will reach the lung and initiate damage. In nonsmokers, the vitamin C (or other water-soluble antioxidant) is likely to be present in sufficient concentration to preclude this damaging process. Indeed, this speculation has been promoted by the American Chemical Society as the subject of a press release in 1997 (Bohm et al. 1997). 

In the United States, the National Council on Radiological Protection and Measurements (NCRP) has recently issued two reports on this subject (NCRP, 1984a,b). The lifetime risks have been estimated and it is predicted that exposures of 2 WLM/y would reduce the probability of living to age 70 by 1.5 and an exposure level of 5 WLM/y would reduce that probability by 4 (NCRP, 1984a). For an average dose to the population of 0.2 WLM/y, the model predicts about 9000 deaths from lung cancer per year in the U.S. population (NCRP, 1984b) for nonsmokers. 

Welders are typically exposed to a complex mixture of dust and fume of metallic oxides, as well as irritant gases, and are subject to mixed-dust pneumoconiosis with possible loss of pulmonary function this should not be confused with benign pneumoconiosis caused by iron oxide. Although an increased incidence of lung cancer has been observed among hematite miners exposed to iron oxide, presumably owing to concomitant radon gas exposure, there is no evidence that iron oxide alone is carcinogenic to man or animals. ... 

In the Montreal case-control study carried out by Siemiatycki (1991) (see monograph on dichloromethane in this volume), the investigators estimated the associations between 293 workplace substances and several types of cancer. Isocyanates were one of the substances, and it was stated that the most common form in this study was toluene diisocyanates. The main occupations to which isocyanate exposure was attributed in this study were motor vehicle refinishers, motor vehicle mechanics and foundry workers. Only 0.8% of the study subjects had ever been exposed to isocyanates. For most types of cancer examined (oesophagus, stomach, colon, rectum, pancreas, prostate, bladder, kidney, skin melanoma, lymphoma), there was no indication of an excess risk due to isocyanates. For lung cancer, in the population subgroup of French Canadians (the majority ethnic group in this region), based on 10 cases exposed at any level, the odds ratio was 2.2 (90% CI, 0.9-5.3). [The interpretation of the null results has to take into account the small numbers and presumably low exposure levels. Workers had multiple exposures.]... 

The trace element threat must be defined in quantitative as well as qualitative terms. It is no easy matter when one considers the number of years it took to establish the relationship between cigarette smoking and lung cancer, where statisticians had the luxury of a control group and groups of graded exposures with which to establish a dose-response relationship. The identity of the carcinogen (s) is still a subject of controversy. 

However, in the skin, vitamin D is also activated by oxidation, and an excess of quenching of this oxidation, due to high concentrations of /3-carotene in the skin, may reduce the amount of vitamin D availability. This is not only important for bone construction, but also because vitamin D represents a powerful natural anticancer agent. This can be an explanation why an increase of lung cancer was found in Finland (country with relative lack of sun), where smoking people and subjects with asbestosis were treated with /3-Carotene and Retinol Efficacy Trial. Concomitantly in ATBC, ischemic episodes were more severe due to the very high dosage of /3-carotene, which can become pro-oxidant. 

A method has been proposed for the determination of cellular levels in lung cancer cell lines of the TKIs dasatinib and lapatinib [141], Cellular samples were extracted with a mixture of tert-butyl methyl ether/ACN/ammonium formate pH 3.5 (6 2 1, v/v/v). The organic layer was subjected to evaporation and the samples were reconstituted in acetonitrile, followed by chromatographic separation on a C18 column. Dasatinib and lapatinib were monitored by tandem MS equipped with a positive electrospray ionization interface in positive ion mode. These cellular experiments showed that lapatinib is not actively expelled from P-gp over-expressing cancer cells, while P-gp activity significantly decreases cellular levels of dasatinib [141],... 

A cohort of 3,408 workers from four former facilities that produced chromium compounds from chromite ore in northern New Jersey was assembled in 1990-1991 using social security records (Rosenman and Stanbury 1996). The subjects were known to have worked in the four facilities sometime between 1937 and 1971, when the last facility closed. Exposure durations ranged from less than 1 year to greater than 20 years. The overall risk of lung cancer derived from proportionate cancer mortality ratios (PCMR) was 1.51 for white males and 1.34 for black males. The risk increased with duration of employment and latency since time of first employment. The cancer mortality ratio for greater than 20 years of workplace exposure and greater than 20 years since first exposure was 194 and 308 for white and black males, respectively. This study also showed significantly increased risk for nasal cavity/sinus cancer indicated... 

There has been some success with vitamin A and its derivatives for treatment of certain types of cancer (Niles, 2000). However, the use of P-carotene as a therapeutic agent suffered a setback when the results from two of three large human intervention studies indicated that high doses of P-carotene caused an increased risk of lung cancer in smokers and subjects exposed to asbestos. This increased risk is thought to be due to metabolites associated with high doses of p-carotene in the presence of smoke (Russell, 2004). 

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