Transplacental inhibitory effect of carrot juice on the clastogenicity of cyclophosphamide in mice

Abstract

Genetic damage during the prenatal period can provoke important neoplastic alterations and other diseases in postnatal life. Beta-carotene (ßC) is considered to be one of the most important anticarcinogens in the diet and can protect mammalian cells against genotoxic events. As carrots are important dietary source of ßC, we decided to test the effect of fresh carrot juice (CaJ) on cyclophosphamide (CP)-induced genotoxicity in maternal and fetal erythropoietic tissues. The treatment with CaJ started on the 7th day of the pregnancy of BALB/c female mice. We observed, on the 16th gestational day, that this treatment did not modify the spontaneous frequency of micronucleated polychromatic erythrocytes (mPCE) in the bone marrow of the females nor in the livers of their fetuses. The mPCE frequency observed 24 h after an intraperitoneal injection of CP (40 mg/kg) on the 15th day was significantly lower in CaJ-pretreated pregnant female bone marrow and in the liver of their fetuses than those observed in the group treated with CP only. These results demonstrate the presence of natural anticlastogens in carrots.<br>O dano genético durante o período pré-natal pode ser uma importante fonte de alterações neoplásicas e de outras doenças durante a vida pós-natal. O beta-caroteno (ßC) é considerado um dos mais importantes anticarcinógenos da dieta e pode proteger células de mamíferos contra eventos genotóxicos. Como a cenoura é a fonte clássica do ßC, nós decidimos testar a modulação do suco de cenoura fresco (CaJ) sobre a genotoxicidade induzida pela ciclofosfamida (CP) no tecido eritropoiético materno e fetal. O tratamento de fêmeas BALB/c com o CaJ ocorreu desde o 7º dia gestacional. Nós observamos, no 16º dia gestacional, que tal tratamento não modificou a freqüência espontânea de eritrócitos policromados micronucleados (mPCE) na medula óssea materna ou no fígado fetal. Quando fêmeas prenhes pré-tratadas com o CaJ receberam uma injeção intraperitoneal de CP (40 mg/kg) no 15º dia gestacional, 24 h depois foi observada uma freqüência de mPCE significativamente menor do que a observada no grupo tratado somente com a CP, tanto na medula óssea materna como no fígado fetal. Estes resultados indicam a presença de anticlastógenos naturais na cenoura

Antimutagenic effects of red apple and watermelon juices on cyclophosphamide-induced genotoxicity in mice

“…The proportion of PCE in any of the experimental groups was not statistically different from that of the negative control group animals, which suggested that intraperitoneal injection of CP alone or following pre-treatment with red apple or watermelon juice did not induce erythropoietic cell toxicity. The observation of non-induction of erythropoietic cell toxicity in mice after intraperitoneal injection of 40 mg/kg body weight of CP was similar to that of Gimmler-Luz et al (1999). The fruit juices that were used in the present study were complex mixtures, containing varying concentrations of all or some of vitamin C, vitamin E, various carotenoids, flavonoids, phenolics (quercetin, anacardic acids and tannin), glutathione, rutin, lutein, lycopene, metals etc, as biologically active compounds (Knekt et al, 1996;Isabelle et al, 2007;Charoensiri et al, 2009).…”

“…The frequency of MNPCE of the positive control group that received only CP injection and the experimental groups, that received CP injection after pre-treatment with red apple or watermelon juices were statistically higher than those of the negative control group (p<0.05). In a similar study, CP induced a significantly higher frequency of chromosome aberrations in adult mouse bone marrow compared to the negative control (Gimmler-Luz et al, 1999). Pretreatment of the mice with the fruit juices reduced the frequency of CP-induced MNPCE, which achieved the level of statistical significance (P≤0.05) for 100% apple juice and 25% watermelon juice only.…”

“…However, there is an increasing literature on the protective role of dietary tocopherol, ascorbate, and ß-carotene in lowering the incidence of a wide variety of human cancers (Byers and Perry, 1992). Consumption of naturally occurring compounds can modify the mutagenic and carcinogenic effects of environmental contaminants (Gimmler-Luz et al, 1999). The mutagenic activities of the tetracyclic nitroarenes 3-nitrofluoranthene (3-NFA) and l-nitropyrene (1-NP) in Salmonella typhimurium TA98 were reduced by β-carotene, retinol, retinal, retinoic acid, retinol palmitate, riboflavin 5′-phosphate, α-tocopherol, vitamins B 12 , C, K 1 and K 3 , as well as biliverdin, bilirubin, chlorophyll, chlorophyllin and haemin (Tang and Edenharder, 1997).…”

“…Mutagenic and antimutagenic activities have been correlated with the presence of certain phytochemical substances such as compounds of the flavonoid group (Brown, 1980;Edenharder et al, 1993); and these metabolites could be involved in mutagen deactivation (Horn and Vargas, 2003). In vivo studies, however, give some contradictory results, perhaps due to the use of different species and administration routes (Gimmler-Luz et al, 1999). In mice, β-carotene protected bone marrow cells against the genotoxic effect of cyclophosphamide (Salvadori et al, 1992).…”

Modulation of Mutagen-Induced Genotoxicity by two Lesotho Medicinal Plants in Allium cepa L

“…Phytochemicals are thought to act as a proton sink that synergistically bring about the antioxidant and free radical scavenging potentials observed (Alisi et al, 2011;Ndhlala et al, 2013). Many studies have also shown that the consumption of naturally occurring compounds can modify the mutagenic and carcinogenic effects of environmental contaminants (Debisri & Archana, 1996;Gimmler-Luz et al, 1999).…”