Background: Lung cancer incidence is gradually leveling off in U.S. men but is continuing to rise in U.S. women. This increase in U.S. women exceeds that expected from a slower decline of smoking among women. Recent epidemiologic and biochemical studies suggest gender differences in susceptibility to tobacco carcinogens. Purpose: We conducted an up-to-date, more in-depth evaluation of our earlier observation of a potential gender difference in relative risk (RR) of lung cancer due to smoking. We added information from several additional case and control subjects and included more precise histologic classification of the cancer type, accurate quantitation of smoke exposure, and adjustments for body size. Methods: The present investigation was a part of an ongoing hospital-based, case-control study by the American Health Foundation. It included data from 1889 case subjects (1108 males and 781 females) with lung cancer of squamous/epid ermoid, small-cell/oat cell, large-cell, and adenocarcinoma types and 2070 control subjects (1122 males and 948 females) with diseases unrelated to smoking. The case and control subjects were admitted to participating hospitals from 1981 to 1994 and were pair-matched by age, sex, hospital, and the time of hospital admission. Ex-smokers and non-Caucasians were excluded from analyses to avoid confounding. The RRs and 95% confidence intervals were estimated from adjusted odds ratios (ORs) by use of unconditional multiple logistic regression analysis, and statistical significance was determined by two-sided tests. The ORs for major histologic types were estimated at increasing levels of exposure to cigarette smoke. Results: Our results indicated that women were more likely to be never-smokers than men, particularly those with the squamous/epidermoid-type cancer (8.3% for women versus 2.9% for men 55 years old or older). Men started smoking earlier, reported inhaling more deeply, and smoked more cigarettes per day than women. In contrast, dose-response ORs over cumulative exposure to cigarette smoking were 1.2-fold to 1.7-fold higher in women than in men for the three major histologic types; these dif

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Differences in Lung Cancer Risk Between Men and Women: Examination of the Evidence

Metal-induced oxidative stress and signal transduction.

Laboratory and clinical reports about the pathogenesis of the carcinogenicity and allergenicity of chromium compounds published between 1985 and 2000 have been reviewed as a basis for consideration of the pathogenetic mechanisms involved. There is good evidence from the clinic and the laboratory that Cr[VI] is the ion responsible for most of the toxic actions, although much of the under lying molecular damage may be due to its intracellular reduction to the even more highly reactive and short-lived chemical species Cr[III] and Cr[V]. Exposure to Cr[VI] can result in various point mutations in DNA and to chromosomal damage, as well as to oxidative changes in proteins and to adduct formation. The relative importance of these effects of chromium ions and of the free oxidising radicals they may generate in the body in causing tumours and allergic sensitisation remain to be demonstrated. Biochemical studies of the DNA-damaging effects and of the pathogenesis of the allergic reactions to chromium ions have not ...

Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000

This public health statement tells you about chromium and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Chromium has been found in at least 1,127 of the 1,699 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which chromium is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may be harmful.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to chromium, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), the form (chromium VI as opposed to chromium III), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

Toxicological Profile for Chromium

Chromium is one of the major inorganic environmental pollutants, which is added in the environment through various natural and anthropogenic activities and exists mainly in two forms: Cr(III) and Cr(VI). Cr(VI) is considered to be more toxic than Cr(III) due to its high solubility and mobility. It is a well-reported occupational carcinogen associated with lung, nasal, and sinus cancers. Thus, this review article provides the detailed information on the occurrence, sources of chromium contamination in the environment and their toxicological effects in human, animal, plants as well as in microorganisms, and bioremediation strategies to minimize the toxic effects.

Toxic and genotoxic effects of hexavalent chromium in environment and its bioremediation strategies

Mutagenicity and disposition of chromium

The production of reactive oxygen species on addition of hexavalent chromium (potassium dichromate, K2Cr2O7) to lung cells in culture was studied using flow cytometer analysis. A Coulter Epics Profile II flow cytometer was used to detect the formation of reactive oxygen species after K2Cr2O7 was added to A549 cells grown to confluence. The cells were loaded with the dye, 2',7'-dichlorofluorescein diacetate, after which cellular esterases removed the acetate groups and the dye was trapped intracellularly. Reactive oxygen species oxidized the dye, with resultant fluorescence. Increased doses of Cr(VI) caused increasing fluorescence (10-fold higher than background at 200 microM). Addition of Cr(III) compounds, as the picolinate or chloride, caused no increased fluorescence. Electron paramagnetic resonance (EPR) spectroscopic studies indicated that three (as yet unidentified) spectral "signals" of the free radical type were formed on addition of 20, 50, 100, and 200 microM Cr(VI) to the A549 cells in suspension. Two other EPR "signals" with the characteristics of Cr(V) entities were seen at field values lower than the standard free radical value. Liver microsomes from male Sprague-Dawley rats treated intraperitoneally with K2Cr2O7 (130 mumole/kg every 48 hr for six treatments) had decreased activity of cytochromes P4503A1 and/or 3A2, and 2C11. Hepatic microsomes from treated female Sprague-Dawley rats, in contrast, had increased activities of these isozymes. Lung microsomes from male Sprague-Dawley rats had increased activity of P4502C11.

In vivo effects of chromium.

Hexavalent chromium [Cr(VI)] compounds are recognized mutagens and carcinogens (IARC, 1980), although the mechanism of action is unknown. Chromium compounds commonly exist in the Cr(VI) and trivalent ([Cr(III)] states, with the Cr(III) state as the most stable form of chromium. Cr(III) compounds differ from Cr(VI) not only in that they are more stable but they exist as cations in octahedral form (with six ligands) and cannot cross membranes readily. They are considered to be non-bioavailable and non-carcinogenic. Cr(VI) compounds, which exist as the oxides or the oxyanions and thus readily cross membranes, are rapidly reduced in the body (both intra- and extracellularly) to the stable Cr(III) via Cr(V) and Cr(IV). Some synthetic Cr(III) complexes, with lipid soluble organic anions as ligands such as the picolinate, cross membranes fairly readily. Cr(III) complexes formed in situ gain entry to the nucleus, as only Cr(III) is detected bound to DNA. Thus it may be that only the Cr(III) formed in situ is toxic. Cr(VI) compounds are not mutagenic without metabolic reduction, (Petrilli and De Flora, 1978). The intermediates, Cr(V) and Cr(IV), are being investigated as putative toxins/carcinogens of Cr(VI). Cr(V) has been detected by electron paramagnetic resonance (EPR) on reduction of Cr(VI) in cells in culture and in vitro (O’Brien et al., 1981; Goodgame and Joy, 1986; Shi and Dalai, 1988; Aiyar et al., 1988;Sugiyama, 1991; Witmer et al., 1994). Both Cr(V) and Cr(IV) can disproportionate so that the reduction of Cr(VI) is not a straightforward process, A two-electron reduction of Cr(VI) is catalyzed by DT diaphorase, which also decreases the mutagenicity of Cr(VI) in vitro.

Hyoung-Sook Park

Papers

Mutagenicity and disposition of chromium

In vivo effects of chromium.

Some activities of the oxidant chromate.