Effects of Micro- and Nano-sized Iron Particles on Colonic Pre-neoplastic Lesions in an Experimental Mouse Model
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Although iron (Fe) plays a crucial role in our body, iron-overload can cause harmful effects such as cancer and aging via promoting the production of free radicals. The effects of orally administered micro-Fe and nano-Fe on colon carcinogenesis were investigated in male ICR mice. After acclimation for 1 week, six-week old mice received 3 i.p. injections (0-2nd weeks of the experiment) of azoxymethane (AOM, 10 mg/kg b.w.), followed by 2% dextran sodium sulfate (DSS)-containing drinking water for the next 1 week to induce aberrant crypt foci (ACF). Animals were fed on AIN-76A purified rodent diet (34.25 Fe mg/kg diet) for 8 weeks. In addition, each group of animals was orally treated with saline alone, carboxymethylcellulose (CMC)+micro-Fe mineral or CMC+nano-Fe mineral daily for 8 weeks. The daily doses were 48 ppm iron for control group and 480 ppm iron for micro-Fe and nano-Fe groups. After the colonic mucosa were stained with methylene blue, aberrant crypt foci (ACF) and aberrant crypts (AC) were counted. Lipid peroxidation in serum and liver was evaluated by the thiobarbituric acid-reactive substances (TBARS) assay. The numbers of ACF and total AC per cm2 of colon significantly increased in nano-Fe group (ACF: 15.74, AC: 23.44) compared to the control group (ACF: 8.69, AC: 16.60) or micro-Fe group (ACF: 11.20, AC: 17.10) (p<0.05). TBARS values in serum and liver significantly increased in micro-Fe and nano-Fe groups compared with the control group (p<0.05). The iron levels in the micro-Fe group and the nano-Fe group were significantly higher than the control group as determined by the ICP method (p<0.05). These results suggest that additionally administrated micro-Fe and nano-Fe can affect the colon carcinogenesis in a mouse model. In addition, the nano-Fe may be more harmful than the micro-Fe in colon carcinogenesis.
Abstract
Although iron (Fe) plays a crucial role in our body, iron-overload can cause harmful effects such as cancer and aging via promoting the production of free radicals. The effects of orally administered micro-Fe and nano-Fe on colon carcinogenesis were investigated in male ICR mice. After acclimation for 1 week, six-week old mice received 3 i.p. injections (0-2nd weeks of the experiment) of azoxymethane (AOM, 10 mg/kg b.w.), followed by 2% dextran sodium sulfate (DSS)-containing drinking water for the next 1 week to induce aberrant crypt foci (ACF). Animals were fed on AIN-76A purified rodent diet (34.25 Fe mg/kg diet) for 8 weeks. In addition, each group of animals was orally treated with saline alone, carboxymethylcellulose (CMC)+micro-Fe mineral or CMC+nano-Fe mineral daily for 8 weeks. The daily doses were 48 ppm iron for control group and 480 ppm iron for micro-Fe and nano-Fe groups. After the colonic mucosa were stained with methylene blue, aberrant crypt foci (ACF) and aberrant crypts (AC) were counted. Lipid peroxidation in serum and liver was evaluated by the thiobarbituric acid-reactive substances (TBARS) assay. The numbers of ACF and total AC per cm2 of colon significantly increased in nano-Fe group (ACF: 15.74, AC: 23.44) compared to the control group (ACF: 8.69, AC: 16.60) or micro-Fe group (ACF: 11.20, AC: 17.10) (p<0.05). TBARS values in serum and liver significantly increased in micro-Fe and nano-Fe groups compared with the control group (p<0.05). The iron levels in the micro-Fe group and the nano-Fe group were significantly higher than the control group as determined by the ICP method (p<0.05). These results suggest that additionally administrated micro-Fe and nano-Fe can affect the colon carcinogenesis in a mouse model. In addition, the nano-Fe may be more harmful than the micro-Fe in colon carcinogenesis.
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