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Nonylphenol (NP) is a breakdown product of nonylphenol ethoxylates, which are used in a variety of industrial, agricultural, household cleaning, and beauty products. NP is one of the most commonly found toxicants in the United States and Europe and is considered a toxicant of concern because of its long half-life. NP is an environmental estrogen that also activates the pregnane X-receptor (PXR) and in turn induces P450s. No study to date has examined the gender-specific effects of NP on hepatic P450 expression. We provided NP at 0, 50 or 75 mg/kg/day for 7 days to male and female FVB/NJ mice and compared their P450 expression profiles. Q-PCR was performed on hepatic cDNA using primers to several CYP isoforms regulated by PXR or its relative, the constitutive androstane receptor (CAR). In female mice, NP induced Cyp2b10 and Cyp2b13, and downregulated the female-specific P450s, Cyp3a41 and Cyp3a44. In contrast, male mice treated with NP showed increased expression of Cyp2a4, Cyp2b9, and Cyp2b10. Western blots confirmed induction of Cyp2b subfamily members in both males and females. Consistent with the Q-PCR data, Western blots showed dose-dependent downregulation of Cyp3a only in females and induction of Cyp2a only in males. The overall increase in female-predominant P450s in males (Cyp2a4, 2b9) and the decrease in female-predominant P450s in females (Cyp3a41, 3a44) suggest that NP is in part feminizing the P450 profile in males and masculinizing the P450 profile in females. Testosterone hydroxylation was also altered in a genderspecific manner, as testosterone 16α-hydroxylase activity was only induced in NP-treated males. In contrast, NP-treated females demonstrated a greater propensity for metabolizing zoxazolamine probably due to greater Cyp2b induction in females. In conclusion, NP causes gender-specific P450 induction and therefore exposure to NP may cause distinct pharmacological and toxicological effects in males compared to females.

Whole cells and peptidoglycan isolated from cell walls of the cyanobacterium Anabaena flos-aquae were lyophilized and used at pH 2 and pH 5 in Cu(II) binding studies. X-ray absorption spectra measured at the Cu K-edge were used to determine the oxidation states and chemical environments of Cu species in the whole-cell and peptidoglycan samples. In the whole-cell samples, most of the Cu retained at both pH values was coordinated by phosphate ligands. The whole-cell fractions contained significant concentrations of Cu(I) as well as Cu(II). An X-ray absorption near-edge spectrum analysis suggested that Cu(I) was coordinated by amine and thiol ligands. An analysis of the peptidoglycan fractions found that more Cu was adsorbed by the peptidoglycan fraction prepared at pH 5, due to increased chelation by amine and carboxyl ligands. The peptidoglycan fractions, also referred to as the cell wall fractions, contained little or no Cu(I). The Cu loading level was 30 times higher in the cell wall sample prepared at pH 5 than in the sample prepared at pH 2. Amine and bidentate carboxyl ligands had similar relative levels of importance in cell wall peptidoglycan samples prepared at both pH values, but phosphate coordination was insignificant.Heavy metals damage the environment since they are nonbiodegradable and have toxic effects on plants, animals, and humans. Precipitation, coagulation, membrane-based processes, and ion exchange are some of the current approaches to the remediation of contaminated sites, but these methods are expensive and lose effectiveness as metal concentrations fall (54). The use of microbes for the bioremediation of trace metals has shown potential for enabling a site to meet regulatory specifications. Experiments have demonstrated the ability of bacteria to immobilize and concentrate metal ions (6,14,28,37,46).Mechanisms by which cells accumulate, sequester, and detoxify metals have been investigated. One indirect approach has been the determination of uptake and retention as a function of pH or competition with some other cation (14,16,20,35). Another has been to chemically modify plant or cell matter (for example, by esterification) to render specific classes of prospective ligands unavailable and to evaluate the impact on metal binding capacity (7,21). In a study of binding sites in cell walls of gram-positive bacteria, teichoic acid, presenting phosphate sites, was extracted with aqueous alkali in order to quantify its contribution to metal binding (7).The chemical studies described are informative but involve many assumptions due to the complexity of biological systems. Also, because of that complexity, few analytical probes can illuminate the chemistry of metals associated with cells. X-ray absorption spectroscopy (XAS) is element specific, returning information for a single atomic number in an arbitrarily complicated mixture (52). XAS is nondestructive, and no sample reduction or digestion is required which would alter the chemistry of the element of interest. XAS can be used to determine the ...

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