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Polymorphic xenobiotic metabolizing enzymes such as N-acetyltransferase 2 (NAT2) or glutathione S-transferase M1 (GSTM1) are known to modulate bladder cancer risk. As no apparent data were available from Hungary, a former member of the eastern European economic organization, a study was performed in Budapest. In total, 182 bladder cancer cases and 78 cancer-free controls were investigated by questionnaire. Genotypes of NAT2, GSTM1, GSTT1, rs1058396 and rs17674580 were determined by standard methods. Current smokers' crude odds ratio (OR) (3.43) and former smokers crude OR (2.36) displayed a significantly increased bladder cancer risk. The risk rose by a factor of 1.56 per 10 pack years. Exposure to fumes was associated with an elevated bladder cancer risk (23% cases, 13% controls). Sixty-four % of the cases and 59% of controls were slow NAT2 acetylators. It was not possible to establish a particular impact of NAT2*6A and *7B genotypes (15 cases, 8%, 5 controls, 7%). GSTT1 exerted no marked influence on bladder cancer (negative 21% cases vs. 22% controls). The portion of GSTM1 negative bladder cancer patients was increased (63% cases vs. 54% controls). The SLC14A1 SNPs rs1058396[AG/GG] and the nearby rs17674580[CT/TT] occurred more frequently in cases (79% and 68%) than controls (77% and 55%). The portion of GSTM1 negative bladder cancer patients is comparable with portions reported from other industrialized areas like Lutherstadt Wittenberg/Germany (58%), Dortmund/Germany (70%), Brescia/Italy (66%) or an occupational case-control series in Germany (56%). Data indicate that GSTM1 is a susceptibility factor for environmentally triggered bladder cancer rather than for smoking-mediated bladder cancer.

The human organic anion transporter 1 (hOAT1) facilitates the basolateral entry of organic anions such as endogenous metabolites, xenobiotics, and drugs into the proximal tubule cells. In the present study we investigated the general occurrence of hOAT1 isoforms in the kidneys and performed functional characterizations. Kidney specimens of 10 patients were analyzed by reverse transcription-polymerase chain reaction. We detected hOAT1-2 as the main transcript in almost all patients, and weak transcripts of hOAT1-1, hOAT1-3, and hOAT1-4 in many of them. An evaluation of the renal distribution showed all four mRNAs mostly restricted to the cortex. Western blot analysis of membrane fractions from two kidney specimens yielded two bands corresponding to the observed mRNA expression, suggesting hOAT1-3 and hOAT1-4 to be expressed on the protein level in vivo. This observation is further supported by immunofluorescence analyses of all four cloned hOAT1 isoforms transiently transfected in COS 7 cells. Functional characterizations did not show any transport activity of hOAT1-3 and hOAT1-4 for the tested substrates. Cotransfection studies of each of them with hOAT1-1 did not alter fluorescein uptake indicating no regulatory impact of these isoforms. Further functional comparisons of hOAT1-1 and hOAT1-2 in fluorescein uptake studies exhibited almost identical affinities for fluorescein with Michaelis constants of 11.6 +/- 3.7 microM (hOAT1-1) and 11.9 +/- 6.4 microM (hOAT1-2), and similar sensitivities to inhibition by p-aminohippurate [IC(50): 16 microM (hOAT1-1), 10 microM (hOAT1-2)], urate [IC(50): 440 microM (hOAT1-1), 385 microM (hOAT1-2)], and furosemide (IC(50): 14 microM (hOAT1-1), 20 microM (hOAT1-2)], implying functional equivalence.

The onion fly Delia antiqua is a specialist herbivore attacking only onions and closely related Allium species. n-Dipropyl disulfide (Pr2S2) has long been known to be attractive to onion flies in the laboratory and in the field. However, the insect's response is highly variable. Using behavioral bioassays we found that Pr2S2 was highly attractive to gravid, mated female onion flies,but did not stimulate oviposition. The response of female onion flies was concentration dependent. The physiological state of the flies (i.e., age, mating status, egg load/oviposition experience) also affected their responsiveness. The response of both sexes of onion flies varied with age, but females were always more strongly attracted than males. Responsiveness of females increased during the first 10 days after emergence. It stayed at a high level until 21 days after which the experiment was terminated. The responsiveness of males reached a maximum at 6-7 days after which it declined. Mated, gravid females responded more strongly to Pr2S2 than unmated, gravid females. Females deprived of the opportunity to oviposit were more attracted compared to females that had oviposited on cut onions prior to the experiment. Electroantennograms (EAG) of females revealed a higher response to stimulation compared to males. The EAG-response of females was not affected by mating status.

Our previous studies have shown that a pre-treatment of rats with triiodothyronine (T3) or dexamethasone (DEXA) increases renal PAH excretion significantly. This stimulation was accompanied by an enhanced protein synthesis within the renal cortex. To explore the molecular basis for this sub-chronic induction process, we investigated the stimulation of PAH accumulation in renal cortical slices as well as the expression level of organic anion transporter 1 (OAT1), the recently cloned renal basolateral PAH-transporter, using RT-PCR techniques under the applied conditions. 10- and 55-day-old Han:WIST rats were treated in vivo with T3 (20 microg/100 g b.wt.) or DEXA (60 microg/100 g b.wt.), both for 3 days, once daily. Renal cortical slices were incubated for 2 hours in Cross-Taggart medium and PAH uptake into kidney tissue was measured time dependently (slice to medium ratio, QS/M). The accumulation capacity is comparable between immature and mature rats (control-QS/M: 6.7 +/- 0.1 vs. 6.9 +/- 0.2, respectively). Both age groups showed a significant increase of PAH accumulation capacity after T3 treatment (10-day-old rats: 15.0 +/- 0.2; 55-day-old rats: 11.7 +/- 1.3). After DEXA pre-treatment, PAH accumulation was only slightly changed (10-day-old rats: 5.9 +/- 0.2; 55-day-old rats: 8.2 +/- 1.3). Semi-quantitative measurements of OAT1 mRNA expression level showed a significant increase of OAT1 mRNA after pre-treatment with both T3 and DEXA in the two age groups. Thus, this is the first evidence that T3 and DEXA pre-treatment induces the expression of OAT1.

Factors affecting the efficacy of an attracticide strategy for the control of the codling moth Cydia pomonella L (Lepidoptera: Tortricidae) were investigated using laboratory and field experiments. The sex-pheromone-based insect-control strategy utilises 100-microliters droplets of a sticky, paste-like formulation containing 1 mg g-1 (E,E)-8,10-dodecadien-1-ol (codlemone) as an attractant for male moths and 40 mg g-1 cyfluthrin, a contact insecticide, applied to branches in the upper parts of the tree crown. The longevity of the treatment under field conditions was assessed in the laboratory by biological testing of variously aged samples of the attracticide formulation which had been applied to the bark of apple trees growing in commercial orchards. Electroantennogram responses of male moth antennae were used to compare codlemone release from the attracticide after different lengths of environmental exposure. Changes in insecticidal efficacy of the same samples were assessed with reference to the speed of knockdown (KT50) and the mortalities after 48 h among populations of male moths confined in cages containing samples of fresh and field-aged formulations. Gradual declines in both the amount of pheromone released and insecticidal activity were observed over the 10-week period of the experiments. Various factors associated with the behaviour of codling moths in the field which might influence the attracticide strategy were also investigated. Although the vertical position of attracticide sources within apple trees had a strong influence on their attractiveness, their horizontal position had none. Results of field trials showed that efficacy of the attracticide depends on the population density of the pest. Under the conditions of the current study a density of three or more sources per tree (= 4500 sources per ha) was required to attain satisfactory levels of codling moth control.

Electroantennograms (EAGs) recorded from the antennae of male Cydia pomonella L. in response to stimulation with doses of the main sex pheromone component E8,E10-dodecadienol (Codlemone) ranging from 5ng to 500&mgr;g did not differ in their amplitudes from responses obtained to a synthetic 7-component pheromone blend containing the same absolute quantities of Codlemone. Based on differences in spike amplitudes obtained in Single Cell recordings (SCR), Sensilla trichodea on the antenna of males were found to contain at least three receptor neurone types. Two olfactory receptor neurones were tuned to Codlemone, while the third failed to be stimulated by Codlemone or by the minor components of the pheromone blend. As spike activity of the neurones in the S. trichodea stimulated by the 7-component blend did not differ from that of stimulation by Codlemone alone it appears that none of the receptor neurones is sensitive to any of the minor components tested. Scanning-electron-microscopical (SEM) examination of Sensilla auricillica on the antennae of Cydia males revealed two morphologically distinct types: rabbit eared shoehorn and regular shoehorn. SCR from these sensilla showed that only olfactory receptor neurones located in the rabbit-eared shoehorn type were tuned to the minor components. Differences in spike amplitudes (large, intermediate, small) allowed three types of neurones to be distinguished. Only the spike frequency of the intermediate receptor neurone was increased by application of the minor components E8-dodecenol, E9-dodecenol, dodecanol, tetradecanol, hexadecanol and E8,E10-dodecadienal. None were stimulated by Codlemone. These results are discussed in relation to the behavioural role of the minor pheromone components of C. pomonella.