Differential protection of chlorophyllin against clastogenic effects of chromium and chlordane in mouse bone marrow in vivo.
TL;DR: The anticlastogenic activity of sodium-copper-chlorophyllin was tested against two known clastogens, chromium(VI) oxide and the pesticide chlordane, both of which occur as environmental toxicants.
About: This article is published in Mutation Research Letters.The article was published on 1993-01-01. It has received 51 citations till now. The article focuses on the topics: Chlorophyllin & Chlordane.
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01 Apr 2006-Journal of Environmental Science and Health Part C-environmental Carcinogenesis & Ecotoxicology Reviews
TL;DR: The increases in stomach tumors in both human and animal studies, along with the toxicokinetic, genotoxic, and mechanistic data, suggest that oral exposure to this agent appears to pose a carcinogenic risk.
Abstract: Recent analyses have revealed that 38% of municipal sources of drinking water in California have detectable levels of hexavalent chromium. This observation provided new impetus to characterize the carcinogenic risk associated with oral exposure to hexavalent chromium in drinking water. Notwithstanding the well-characterized increases in cancer associated with inhalation exposure to this chemical, the marked reduction of hexavalent chromium to trivalent chromium in the stomach suggests that exposure to hexavalent chromium in drinking water may not pose a carcinogenic risk. A reevaluation of studies that investigated the toxicokinetics, the genotoxicity, and the mechanism of carcinogenicity of hexavalent chromium, as well as the available human and animal cancer studies, was undertaken to determine if there is evidence that exposure to this chemical in drinking water may pose a carcinogenic risk. Mechanistic studies suggest the potential for a carcinogenic response if hexavalent chromium enters cells. Both toxicokinetic and genotoxicity studies indicate that a portion of an orally administered dose of hexavalent chromium is absorbed and gets into cells of several tissues, causing DNA damage. The only lifetime oral study of hexavalent chromium in animals conducted thus far yielded a statistically significant increase in stomach tumors compared to controls. Also, in a limited-term cancer study, co-exposure to hexavalent chromium in drinking water and ultraviolet light produced skin tumors in mice. The only available cancer study of humans exposed to hexavalent chromium in drinking water revealed a statistically significant increase in stomach tumors. Moreover, a meta-analysis of occupational studies also revealed a statistically significant increase in stomach cancers. The increases in stomach tumors in both human and animal studies, along with the toxicokinetic, genotoxic, and mechanistic data, suggest that oral exposure to this agent appears to pose a carcinogenic risk.
167Â citations
TL;DR: The weight of scientific evidence supports that Cr(VI) is not carcinogenic in humans via the oral route of exposure at permissible drinking-water concentrations.
Abstract: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation, based on elevated rates of lung cancer among occupationally exposed workers in certain industries. Cr(VI) is also genotoxic in bacterial and mammalian cell lines. In contrast, scientific panels in the United States and abroad have reviewed the weight of evidence (WOE) and decided that the available data are insufficient to conclude that Cr(VI) is an oral carcinogen. A criterion of 0.2 ppb was established by a California agency for Cr(VI) in drinking water to prevent cancer, however, this criterion was withdrawn in November, 2001. This criterion was remarkably lower than the promulgated California and federal drinking-water standards for total chromium of 50 ppb and 100 ppb, respectively. Both of the promulgated standards are designed to be protective of humans who ingest Cr(VI). This article describes a WOE analysis to examine the likelihood that Cr(VI) in drinking water poses a cancer hazard at the current U.S. drinking-water standard. The results indicate that: (1) From the historical epidemiological studies, there are a few reports of increased rates of digestive system cancer among Cr(VI)-exposed workers, although most are not statistically significant; (2) the preponderance of evidence from recent epidemiological studies of Cr(VI)-exposed workers does not support an increased risk of cancer outside of the respiratory system; (3) studies of four environmentally exposed populations are negative; (4) there is only one lifetime animal feeding study, and the findings from that study are considered to be flawed and inconclusive; and (5) recent kinetics and in vivo genotoxicity data demonstrate that Cr(VI) is reduced to nontoxic Cr(III) in saliva, in the acidic conditions of the stomach, and in blood. In short, at concentrations at least as high as the current U.S. maximum contaminant level (100 ppb), and probably at least an order of magnitude higher, Cr(VI) is reduced to Cr(III) prior to or upon systemic absorption. The weight of scientific evidence supports that Cr(VI) is not carcinogenic in humans via the oral route of exposure at permissible drinking-water concentrations.
128Â citations
Cites background from "Differential protection of chloroph..."
...Four additional studies (Sarkar et al., 1993; Bagchi et al., 1995a, 1995b; and Devi et al., 2001) reported DNA effects in animals treated orally with Cr(VI) at concentrations near the LD50 and reported some positive findings, primarily in hepatic nuclei....
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TL;DR: An attempt has been made in this article to review the relative efficacy of chlorophyll and chlorophylla in modifying the genotoxic effects of various known toxicants.
Abstract: Reports on an inverse relationship between the consumption of fresh vegetables and human gastrointestinal cancer have been followed by screening for the protective activity of a large number of plant extracts, including leafy vegetables. Chlorophyll is ubiquitous in all green plant parts. Chlorophyllins are derivatives of chlorophyll in which the central magnesium atom is replaced by other metals, such as cobalt, copper or iron. An attempt has been made in this article to review the relative efficacy of chlorophyll and chlorophyllin in modifying the genotoxic effects of various known toxicants.
97Â citations
TL;DR: Retinol, chlorophyllin, and N-acetylcysteine are examined and compared with regard to their antimutagenic activity against some promutagens and a group of direct-acting alkylating agents with emphasis on the xenobiotic metabolizing enzyme systems.
Abstract: In this review, retinol, chlorophyllin, and N-acetylcysteine are examined and compared with regard to their antimutagenic activity against some promutagens and a group of direct-acting alkylating agents. The promutagens included aflatoxin B1, certain polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), and certain heterocyclic amines (e.g., food pyrolysates). Results of antimutagenicity testing selected from data surveyed in the published literature are displayed graphically as activity profiles of antimutagens showing both the doses tested and the extent of inhibition or enhancement of mutagenic activity. All three antimutagens are discussed in terms of their putative mechanisms of action in vitro and in vivo with emphasis on the xenobiotic metabolizing enzyme systems.
87Â citations
TL;DR: The weight of evidence supports the plausibility that Cr (VI) may act through a mutagenic MOA and recommends a linear extrapolation for the oral risk assessment, as well as recommending that the ADAFs be applied.
Abstract: In response to the 2005 revised U.S Environmental Protection Agency's (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with additional information to determine whether the initiating step in carcinogenesis is through a mutagenic mode of action (MOA). This information is necessary to decide if age-dependent adjustment factors (ADAFs) should be applied to the risk assessment. Chromium (VI) [Cr (VI)], a carcinogen in animals and humans via inhalation, was reassessed by the National Toxicology Program (NTP) in 2-year drinking water studies in rodents. From these data, NTP concluded that the results with Cr (VI) showed clear evidence of carcinogenicity in male and female mice and rats. Cr (VI) is also mutagenic, in numerous in vitro assays, in animals (mice and rats) and in humans. Accordingly, Cr (VI) was processed through the MOA framework; postulated key steps in tumor formation were interaction of DNA with Cr (VI) and reduction to Cr (III), mutagenesis, cell proliferation, and tumor formation. Within the timeframe and tumorigenic dose range for early events, genetic changes in mice (single/double-stranded DNA breaks) commence within 24 hr. Mechanistic evidence was also found for oxidative damage and DNA adduct formation contributing to the tumor response. The weight of evidence supports the plausibility that Cr (VI) may act through a mutagenic MOA. Therefore, the Cancer Guidelines recommend a linear extrapolation for the oral risk assessment. Cr (VI) also induces germ cell mutagenicity and causes DNA deletions in developing embryos; thus, it is recommended that the ADAFs be applied.
87Â citations
Cites background or methods from "Differential protection of chloroph..."
..., 2001]; in vivo gene mutations, chromosome aberrations, micronuclei in rats and mice [Shindo et al., 1989; Sarkar et al., 1993; Itoh and Shimada, 1998; GAP, 2000] Mutagenic DNA adducts in human fibroblasts; DNA damage and micronuclei in PBL and buccal epithelial cells of Cr (VI) workers [Benova et al....
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...aberrations 20 mg/kg CrO3/single oral gavage 24 hr Bone marrow (Swiss) 1 Sarkar et al. [1993]...
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References
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479Â citations
TL;DR: The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.
Abstract: Chlorophyllin, the sodium and copper salt of chlorophyll, was tested for its ability to inhibit the mutagenic activity of a variety of complex mixtures--extracts of fried beef, fried shredded pork, red grape juice, red wine, cigarette smoke, tobacco snuff, chewing tobacco, airborne particles, coal dust and diesel emission particles--in strain TA98 of Salmonella typhimurium. Chlorophyllin was highly effective against the mutagenicity (90-100% inhibition) of 8 of these 10 mixtures. The mutagenicity of the other 2 mixtures was inhibited 75-80% at the highest concentration of chlorophyllin studied. Control and reconstruction experiments showed that chlorophyllin was not toxic to Salmonella at the concentrations used. The antimutagenic activity of chlorophyllin was heat-stable. The mechanism of the antimutagenicity of chlorophyllin in these experiments is not known; however, chlorophyllin is an antioxidant. Scavenging of radicals and/or interaction with the active group of mutagenic compounds may be responsible for its antimutagenic activity. The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.
217Â citations
TL;DR: Aqueous and acetone extractions of some common vegetables inhibited the activation of 3-methylcholanthrene and benzo[ a ]pyrene in the Ames Salmonella gene reversion mutagenesis/mammalian microsomal activation assay.
Abstract: Aqueous and acetone extractions of some common vegetables inhibited the activation of 3-methylcholanthrene and benzo[ a ]pyrene in the Ames Salmonella gene reversion mutagenesis/mammalian microsomal activation assay. The potency of the inhibitory activity was correlated with the chlorophyll content of the acetone extracts. The aqueous fractions contained sufficient histidine to interfere with the interpretation of the result. However, grouping the aqueous extracts from vegetables yielding low, medium, and high levels of histidine allowed comparison between antimutagenic activity and chlorophyll content. Increasing chlorophyll contents corresponded to increasing antimutagenic activities in all 3 groups. Sodium copper chlorophyllin demonstrated comparable inhibitory activity when compared at the same chlorophyll level.
140Â citations