Dibutyl Phthalate Treatment Research Articles

Purging effect of dibutyl phthalate on leukemia cells involves fas independent activation of caspase-3/CPP32 protease

We previously found that dibutyl phthalate (DBP) had a pharmacological activity in eliminating tumor cells and could be used as a purging agent in autologous bone marrow transplantation. In this study, we show that DBP can induce apoptosis in MO7e and U937 leukemia cell lines. Treatment of these cells with DBP up-regulates cellular activity of caspase-3/CPP32 and causes apoptosis rapidly as determined by cell viability and dUTP nick end labeling assay. Activation of caspase-3/CPP32 and cleavage of poly(ADP–ribose) polymerase were determined in DBP-induced apopotosis of leukemia cells. However, DBP treatment did not induce the expression of fas. Two caspase inhibitors, z-VAD-fmk and N-acetyl-Asp-Glu-Val-Asp-aldehyde partly blocked the cell death of MO7e cells induced by DBP. These results suggest that fas-independent activation of caspase-3 protease plays important roles in the purging effect of DBP on leukemia cells.

Effects of Dibutyl Phthalate as an Environmental Endocrine Disruptor on Gonadal Sex Differentiation of Genetic Males of the Frog Rana rugosa

To examine the effects of dibutyl phthalate (DBP) on gonadal sex differentiation, genetically male tadpoles of Rana rugosa were exposed to dilute solutions of DBP at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation in R. rugosa. Tadpoles were necropsied on day 40. The genetically male tadpoles were produced from crossings between males (ZZ) of one local population, in which females are the heterogametic sex, and females (XX) of another local population, in which males are the heterogametic sex. As positive control groups, tadpoles were exposed to dilute solutions of 17beta-estradiol (E(2)) at concentrations of 0. 01, 0.1, or 1 microM during the same period. The internal structure of the gonads was histologically examined in a total of 30 control tadpoles, 86 E(2)-treated tadpoles, and 90 DBP-treated tadpoles. The gonads of the control tadpoles all showed the typical structure of testes. In contrast, 0.01, 0.1, and 1 microM E(2) treatments caused the undifferentiated gonads of 18, 63, and 100% of the tadpoles, respectively, to develop into gonads of complete or partial ovarian structure. After 0.1, 1, and 10 microM DBP treatment, 0, 7, and 17% of tadpoles, respectively, were similarly affected. These findings suggest that DBP was about 1,000-fold less potent than E(2). Nevertheless, DBP is an environmentally dangerous hormone that disrupts the pathways of testicular differentiation in genetically male animals.

Effects of dibutyl phthalate as an environmental endocrine disruptor on gonadal sex differentiation of genetic males of the frog Rana rugosa.

To examine the effects of dibutyl phthalate (DBP) on gonadal sex differentiation, genetically male tadpoles of Rana rugosa were exposed to dilute solutions of DBP at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation in R. rugosa. Tadpoles were necropsied on day 40. The genetically male tadpoles were produced from crossings between males (ZZ) of one local population, in which females are the heterogametic sex, and females (XX) of another local population, in which males are the heterogametic sex. As positive control groups, tadpoles were exposed to dilute solutions of 17beta-estradiol (E(2)) at concentrations of 0. 01, 0.1, or 1 microM during the same period. The internal structure of the gonads was histologically examined in a total of 30 control tadpoles, 86 E(2)-treated tadpoles, and 90 DBP-treated tadpoles. The gonads of the control tadpoles all showed the typical structure of testes. In contrast, 0.01, 0.1, and 1 microM E(2) treatments caused the undifferentiated gonads of 18, 63, and 100% of the tadpoles, respectively, to develop into gonads of complete or partial ovarian structure. After 0.1, 1, and 10 microM DBP treatment, 0, 7, and 17% of tadpoles, respectively, were similarly affected. These findings suggest that DBP was about 1,000-fold less potent than E(2). Nevertheless, DBP is an environmentally dangerous hormone that disrupts the pathways of testicular differentiation in genetically male animals.

Molecular function analysis of collapsin-1 in formation of neural network

The potential effects of dibutyl phthalate (DBP) on soil ecosystems and biological processes have recently aroused great concern because of the ubiquitous nature of this pollutant. However, the effects of DBP-associated disturbance on rhizosphere and non-rhizosphere soil microbial communities remain poorly understood. In the present study, we investigated the effects of DBP contamination on microbial function and soil enzyme activities in rhizosphere and non-rhizosphere soils throughout the growing season of wheat. We conducted pot experiments under glasshouse conditions and used different concentrations of DBP: 10, 20, and 40 mg kg–1. We found that the average well color development value and McIntosh index in rhizosphere and non-rhizosphere soils increased in the 10 and 20 mg kg–1 DBP treatments, but declined in the 40 mg kg–1 DBP treatment at the seedling and tillering stages, particularly, in the non-rhizosphere soil. DBP addition enhanced the Shannon-Wiener and Simpson indexes in rhizosphere and non-rhizosphere soils throughout the growing period of wheat. A principal component analysis clearly differentiated the treatments from the control, indicating that DBP led to different patterns of potential carbon utilization in rhizosphere and non-rhizosphere soils. The microbial use of amino acids was significantly increased in rhizosphere and non-rhizosphere soils after DBP addition, while the use of carbohydrates was significantly declined (p < 0.05). The dehydrogenase, urease, and acid phosphatase activities were significantly stimulated (p < 0.05) at the seedling stage, while the phenol oxidase and β-glucosidase activities were inhibited. The 40 mg kg–1 DBP treatment significantly decreased the phenol oxidase and β-glucosidase activities in rhizosphere and non-rhizosphere soils at the seedling stage, particularly in non-rhizosphere soil (p < 0.05). The microbial function and soil enzymatic activities were gradually restored following the wheat growing stage. These results offer a better understanding of the effects of DBP on the activities and functional diversity of microbial communities in farmland soils.

Phthalate esters I: Effects on cytochrome P-450 mediated metabolism in rat liver and lung, serum enzymatic activities and serum protein levels.

Dimethylphthalate (DMP), dibutylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) were given i.p. (3.8 mM/kg) to Sprague Dawley rats for 5 days. DBP increased significantly the liver concentration of cytochrome P-450, but decreased the lung concentration by about 40%. DBP decreased the lung concentration of cytochrome b5 and NADPH-cytochrome-c-reductase activity by about 30%. Only minor effects were seen after treatment with DMP and DEHP. The direction of B(a)P metabolism was changed and the formation of 2- and 3-hexanol metabolites were increased in liver microsomes after DBP treatment. All phthalate esters decreased the lung metabolism of B(a)P. The cytochrome P-450 enzyme system in the lung was ten times more effective than that in the liver as far as metabolism of n-hexane was concerned. Only minor effects were observed in serum enzyme activities, but a significant decrease in the serum level of albumin was observed after treatment with DBP. No relationship was found between the carbon chain length of the investigated chemicals and effects on microsomal enzymatic activities.

Studies on dibutyl phthalate-induced testicular atrophy in the rat: Effect on zinc metabolism

The daily oral administration of dibutyl phthalate (DBP) at 2000 mg/kg for 4 days to young male rats was found to produce testicular injury and loss in organ weight. Additionally, it was found that DBP treatment adversely affected zinc metabolism. The urinary excretion of zinc was increased and the zinc content in the testes was markedly decreased. Moreover; the turnover rate of this element in testicular tissue was substantially enhanced. DBP treatment did not significantly alter the zinc concentrations in the kidney and liver. Investigations using n-butanol, o-phthalic acid, and monobutyl phthalate (MBP), the major metabolite of DBP, showed that testicular effects were reproducible by MBP. Coadministration of zinc was found to afford a substantial measure of protection against testicular damage produced by DBP.