title: Lack of genotoxic effects in hematopoietic and gastrointestinal cells of mice receiving chromium(VI) with the drinking water.
abstract: Chromium(VI) is genotoxic when tested in vitro or injected parenterally in such a way to escape detoxification mechanisms. However, its genotoxicity and potential carcinogenicity are lost, depending on dose and administration route, due to efficient reduction in body fluids and nontarget cells. Chromium(VI) is a Group 1 IARC carcinogen, but only in the respiratory tract and in well-defined occupational settings that involved heavy exposures. Recently, concern has been expressed that oral chromium(VI) may be a gastric carcinogen. We demonstrated that administration of very high doses of chromium(VI) with the drinking water does not induce any clastogenic effect in hematopoietic cells of adult mice and their fetuses. Thereafter, we investigated whether administration of chromium(VI) with the drinking water may induce local genotoxic effects in the gastrointestinal tract. Sodium dichromate dihydrate was administered to mice for 9 consecutive months, at doses corresponding to 5 and 20 mg chromium(VI)/l, which exceed drinking water standards by 100 and 400 times, respectively. Under these conditions, chromium(VI) failed to enhance the frequency of DNA-protein crosslinks and did not cause oxidative DNA damage, measured in terms of 8-oxo-2'-deoxyguanosine, in the forestomach, glandular stomach and duodenum. When cells from the same organs were isolated and challenged in vitro with chromium(VI), as positive controls, the same genotoxicity biomarkers were evidently affected. Thus, consistently with the knowledge accumulated in 50 years of research on chromium(VI) kinetics and metabolism, oral chromium(VI) appears to be devoid of genotoxicity in the gastrointestinal tract. After 9 months, we did not observe any variation of tumor yield in skin, lung, forestomach, glandular stomach, and duodenum of chromium(VI)-treated mice. These results are discussed in the light of literature data, also including a recent 2-year carcinogenicity study performed by the National Toxicology Program.
authors.affiliation: Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy. sdf@unige.it
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Agostini
authors.forename: Roumen
authors.initials: R
authors.lastname: Balansky
authors.forename: Rosanna
authors.initials: R
authors.lastname: Micale
authors.forename: Barbara
authors.initials: B
authors.lastname: Baluce
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental; D002857:Chromium / Q000633:toxicity*; D004326:Drinking; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006413:Hematopoietic System / Q000187:drug effects*; D008431:Maternal-Fetal Exchange; D051379:Mice; D009153:Mutagens; D011247:Pregnancy; D014867:Water / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002274:Carcinogens, Environmental; D009153:Mutagens; D014874:Water Pollutants, Chemical; D014867:Water; D002857:Chromium