Carcinogenicity and metabolic profiles of 6-substituted benzo[a]pyrene derivatives on mouse skin

The ability was tested of appropriate substituents of benzo[a]pyrene (BP) at C-6 to decrease or suppress the carcinogenic activity for these BP derivatives relative to the parent compound. 8-week-old female Swiss mice in 9 groups of 30 were treated on the back with 0.2 mumol of compound in acetone 4 times weekly for 20 weeks. The following compounds were administered: BP, 6-methylbenzo[a]pyrene (BP-6-CH3), 6-hydroxymethylbenzo[a]pyrene (BP-6-CH2OH), benzo[a]pyrene-6-carboxaldehyde (BP-6-CHO), benzo[a]pyrene-6-carboxylic acid, 6-methoxybenzo[a]pyrene, 6-acetoxybenzo[a]pyrene, 6-bromobenzo[a]pyrene, and 6-iodobenzo[a]pyrene. Two additional groups received BP or BP-6-CH3 twice weekly for 20 weeks at a total dose 25% of that above. In addition, the metabolism of selected 6-substituted BP derivatives was studied, using mouse skin homogenates in vitro and mouse skin in vivo. Only four compounds were carcinogenic; the order of potency was BP greater than BP-6-CH3 greater than BP-6-CH2OH and BP-6-CHO. The difference in carcinogenicity between BP-6-CH2OH and BP-6-CHO could not be assessed by this experiment. In a further tumorigenesis experiment the carcinogenicity of BP-6-CH2OH was compared to that of BP-6 CHO, BP-6-CH3 and 6-hydroxymethylbenzo[a]pyrere sulfate ester (BP-6-CH2OSO3Na) on mouse skin. 9-week-old female Swiss mice in groups of 28 were treated at three dose levels with 0.8, 0.2 and 0.05 mumol of compounds in dioxane--dimethyl sulfoxide (75 : 25) twice weekly for 40 weeks. After 40 experimental weeks BP-6-CH2OSO3Na proved to be a more potent carcinogen than BP-6-CH2OH, which, in turn was more active than BP-6-CHO. The greater carcinogenicity of BP-6-CH3 relative to BP-6-CH2OH and BP-6-CHO is confirmed, suggesting that BP-6-CH2OH is not a proximate carcinogenic metabolite for BP-6-CH3. Since BP-6-CHO is a weaker carcinogen than BP-6-CH2OH and is efficiently reduced metabolically to BP-6-CH2OH, the latter compound may be a common proximal carcinogenic metabolite. The stronger potency of BP-6-CH2OSO3Na, compared to its alcohol, suggests that an ester of BP-6-CH2OH might be the ultimate alkylating compound reacting with cellular nucleophiles.     

Leaf age and salinity influence water relations of pepper leaves

Plant growth is reduced under saline conditions even when turgor in mature leaves is maintained by osmotic adjustment. The objective of this study was to determine if young leaves from salt-affected plants were also osmotically adjusted. Pepper plants (Capsicum annuum L. cv. California Wonder) were grown in several levels of solution osmotic potential and various components of the plants' water relations were measured to determine if young, rapidly growing leaves could accumulate solutes rapidly enough to maintain turgor for normal cell enlargement. Psychrometric measurements indicated that osmotic adjustment is similar for both young and mature leaves although osmotic potential is slightly lower for young leaves. Total water potential is also lower for young leaves, particularly at dawn for the saline treatments. The result is reduced turgor under saline conditions at dawn for young but not mature leaves. This reduced turgor at dawn, and presumably low night value, is possibly a cause of reduced growth under saline conditions. No differences in leaf turgor occur at midday. Porometer measurements indicated that young leaves at a given salinity level have a higher stomatal conductance than mature leaves, regardless of the time of day. The result of stomatal closure is a linear reduction of transpiration.     

Reversible protection of Cys-93(β) by PEG alters the structural and functional properties of the PEGylated hemoglobin

As a potential hemoglobin (Hb)-based oxygen carrier (HBOC), the PEGylated Hb has received much attention for its non-nephrotoxicity. However, PEGylation can adversely alter the structural and functional properties of Hb. The site of PEGylation is an important factor to determine the structure and function of the PEGylated Hb. Thus, protection of some sensitive residues of Hb from PEGylation is of great significance to develop the PEGylated Hb as HBOC. Here, Cys-93(β) of Hb was conjugated with 20 kDa polyethylene glycol (PEG20K) through hydrazone and disulfide bonds. Then, the conjugate was modified with PEG5K succinimidyl carbonate (PEG5K-SC) using acylation chemistry, followed by removal of PEG20K Hb with hydrazone hydrolysis and disulfide reduction. Reversible conjugation of PEG20K at Cys-93(β) can protect Lys-95(β), Val-1(α) and Lys-16(α) of Hb from PEGylation with PEG5K-SC. The autoxidation rate, oxygen affinity, structural perturbation and tetramer instability of the PEGylated Hb were significantly decreased upon protection with PEG20K. The present study is expected to improve the efficacy of the PEGylated Hb as an oxygen therapeutic.     

Construction and maintenance of the optimal photosynthetic systems of the leaf, herbaceous plant and tree: an eco-developmental treatise

BACKGROUND AND AIMS: The paper by Monsi and Saeki in 1953 (Japanese Journal of Botany 14: 22-52) was pioneering not only in mathematical modelling of canopy photosynthesis but also in eco-developmental studies of seasonal changes in leaf canopies. SCOPE: Construction and maintenance mechanisms of efficient photosynthetic systems at three different scaling levels--single leaves, herbaceous plants and trees--are reviewed mainly based on the nitrogen optimization theory. First, the nitrogen optimization theory with respect to the canopy and the single leaf is briefly introduced. Secondly, significance of leaf thickness in CO2 diffusion in the leaf and in leaf photosynthesis is discussed. Thirdly, mechanisms of adjustment of photosynthetic properties of the leaf within the herbaceous plant individual throughout its life are discussed. In particular, roles of sugar sensing, redox control and of cytokinin are highlighted. Finally, the development of a tree is considered. CONCLUSIONS: Various mechanisms contribute to construction and maintenance of efficient photosynthetic systems. Molecular backgrounds of these ecologically important mechanisms should be clarified. The construction mechanisms of the tree cannot be explained solely by the nitrogen optimization theory. It is proposed that the pipe model theory in its differential form could be a potential tool in future studies in this research area.     

FATP1 mediates fatty acid-induced activation of AMPK in 3T3-L1 adipocytes

Fatty acid transport proteins are integral membrane acyl-CoA synthetases implicated in adipocyte fatty acid influx and esterification. FATP-dependent production of AMP was evaluated using FATP4 proteoliposomes, and fatty acid-dependent activation of AMP-activated protein kinase (AMPK) was assessed in 3T3-L1 adipocytes. Insulin-stimulated fatty acid influx (palmitate or arachidonate) into cultured adipocytes resulted in an increase in the phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Consistent with the activation of AMPK, palmitate uptake into 3T3-L1 adipocytes resulted in an increase in intracellular [AMP]/[ATP]. The fatty acid-induced increase in AMPK activation was attenuated in a cell line expressing shRNA targeting FATP1. Taken together, these results demonstrate that, in adipocytes, insulin-stimulated fatty acid influx mediated by FATP1 regulates AMPK and provides a potential regulatory mechanism for balancing de novo production of fatty acids from glucose metabolism with influx of preformed fatty acids via phosphorylation of acetyl-CoA carboxylase.     

Effects of RF exposure of teenagers and adults by CDMA cellular phones

Many cellular phone provocation studies have been conducted since the question of increased health risk from extended usage of cellular phones became a social issue. Internationally, most studies have been conducted regarding the effects of GSM cellular phones on blood pressure and heart rate of adult volunteers. On the other hand, very few provocation studies have been conducted regarding the physiological effects of CDMA phones on teenagers. In this study, two volunteer groups consisting of 21 teenagers and 21 adults were exposed to 300 mW of radio frequency (RF) electromagnetic field emitted by a CDMA cellular phone for half an hour. Physiological parameters such as systolic and diastolic blood pressures, heart rate, respiration rate, and skin resistance were simultaneously measured. All the parameters for both groups were unaffected during the exposure except for decreased skin resistance of the teenager group (P < .0001). For the regrouped 23 male and 19 female subjects, all the parameters for both groups were unaffected during the exposure except for decreased skin resistance of the male subjects (P = .0026). Those resistances at 10 min after the terminated exposure returned to the resistances at rest regardless of the different groups of age and sex.     

Association study of AGER gene polymorphism and hypertension in Han Chinese population

Background

Advanced glycation end products (AGEs) are produced by non-enzymatic glycation or glycoxidation of proteins, lipids and nucleic acids. The bond of AGEs and the receptor of AGE (AGER) in a pro-oxidant environment could induce immune and inflammation reaction involved in progress of microvascular disease. Accumulated evidence warrant further study on AGE–AGER pathway and genetic susceptibility to hypertension (HT).

Methods

We designed a two-stage association study to evaluate the association of AGER polymorphism and HT. In stage 1, seven tagSNPs were tested in 524 cases and 531 controls and the significant SNPs (P < 0.05) would enter into stage 2 including 807 cases and 869 controls. Furthermore, joint analysis was performed for all 2731 subjects including 1331 cases and 1400 controls, and meta-analysis was applied to evaluate combined estimations from the subgroups of stage 1 and stage 2.

Results

In stage 1, rs204994 had significant association with HT (P < 0.05) and enter stage 2. Neither joint analysis nor meta-analysis found statistical association of rs204994 with HT after adjusted for the covariates in the whole population. However, further stratification analysis found that rs204994 was significantly associated with HT in < 50 years and ≥ 50 years groups, ORs (95%CI) of dominant model were 1.623 (1.054–2.500) and 0.721 (0.546–0.952) respectively. No significant correlation was found between blood pressure and the polymorphisms of rs204994.

Conclusions

Our data suggests that age might modulate the genetic effects of variation of rs204994 in AGER on HT and further replications in other populations and functional studies should be warranted.     

Identification and characterization of multiple curcumin synthases from the herb Curcuma longa

Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2 and CURS3, that are capable of curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. The availability of the substrates and the expression levels of the three different enzymes capable of curcuminoid synthesis with different substrate specificities might influence the composition of curcuminoids in the turmeric and in different cultivars.