Increase In LC50 Research Articles

Interplay between Cellular Methyl Metabolism and Adaptive Efflux during Oncogenic Transformation from Chronic Arsenic Exposure in Human Cells

After protracted low level arsenic exposure, the normal human prostate epithelial cell line RWPE-1 acquires a malignant phenotype with DNA hypomethylation, indicative of disrupted methyl metabolism, and shows arsenic adaptation involving glutathione overproduction and enhanced arsenic efflux. Thus, the interplay between methyl and glutathione metabolism during this progressive arsenic adaptation was studied. Arsenic-treated cells showed a time-dependent increase in LC50 and a marked increase in homocysteine (Hcy) levels. A marked suppression of S-adenosylmethionine (SAM) levels occurred with decreased methionine adenosyltransferase 2A (converts methionine to SAM) expression and increased negative regulator methionine adenosyltransferase B, suggesting reduced conversion of Hcy to SAM. Consistent with Hcy overproduction, activity and expression of S-adenosylhomocysteine hydrolase (converts S-adenosylhomocysteine to Hcy) were both increased. Expression of cystathionine beta-synthase, a key gene in the transsulfuration pathway, and various glutathione production genes were increased, resulting in a 5-fold increase in glutathione. Arsenic efflux increased along with expression of ATP-binding cassette protein C1, which effluxes arsenic as a glutathione conjugate. Evidence of genomic DNA hypomethylation was observed during early arsenic exposure, indicating that the disruption in methyl metabolism had a potential impact related to oncogenesis. Thus, cellular arsenic adaptation is a dynamic, progressive process that involves decreased SAM recycling and concurrent accumulation of Hcy, which is channeled via transsulfuration to increase glutathione and enhance arsenic efflux but may also impact the carcinogenic process.

Selection and heritability of resistance to Bacillus thuringiensis subsp kurstaki and transgenic cotton in Helicoverpa armigera (Lepidoptera: Noctuidae).

Compared with an unselected susceptible population, a cotton bollworm, Helicoverpa armigera (Hübner), population selected for 22 generations with transgenic cotton leaves (modified Cry1A) in the laboratory developed 11.0-fold resistance to Cry1Ac (one single-protein product MVPII). Resistance to Bacillus thuringiensis Berliner subsp kurstaki (Btk) was selected for 22 generations with a 5.2-fold increase in LC50. The estimated realized heritabilities (h2) of resistance for transgenic-cotton- and Btk-selected populations were 0.1008 and 0.2341, respectively. This reflects the higher phenotypic variation in response to Cry1Ac in the transgenic-cotton-selected population. This variation may have been caused by differences in protein toxin levels expressed in different growth stages of the transgenic cotton. Because of the different slopes of the probit regression lines between Cry1Ac and Btk, the estimated realized h2 cannot be used visually to compare resistance development to Cry1Ac and Btk in H armigera. Thus, the response quotient (Q) of resistance was also estimated. The Q values of resistance for transgenic-cotton- and Btk-selected populations were 0.0763 and 0.0836, respectively. This showed that the rate of resistance development would be similar in both selection populations. This result indicates that the selection of resistance using transgenic cotton is different from that selected using the single toxin. Resistance risk to transgenic cotton and Btk in field populations was assessed assuming different pressures of selection by using the estimated h2. Assuming the h2 of resistance in a field population was half of the estimated h2, and the population received prolonged and uniform exposure to transgenic cotton or Btk causing >70% mortality in each generation, we predicted that resistance would increase 10-fold after <23 generations for Cry1Ac in transgenic cotton-selected-populations and after <21 generations for Btk in Btk-selected populations. Cross-resistance would be expected after <48 generations for Btk in transgenic-cotton-selected populations and after <21 generations for Cry1Ac in Btk-selected population. The results show that the potential to evolve resistance is similar in both transgenic-cotton- and Btk-selected populations, but that cross-resistance development to Btk is slower in transgenic-cotton-selected populations than cross-resistance development to Cry1Ac in Btk-selected populations.

Susceptibility pattern and development of resistance in the diamondback moth,Plutella xylostella L, toBacillus thuringiensis Berl varkurstaki in India

Base-line susceptibility for six-day-old larvae of the diamondback moth, Plutella xylostella, against Bacillus thuringiensis var kurstaki (Biobit®) was studied by a cabbage leaf disc dip bioassay technique. Diamondback moth from 13 locations in seven different states spread over a distance of about 3000 km longitudinally was used for these studies. Forty-eight-hour LC50 values varied from 1.0 to 10.97 mg AI litre−1. Further investigations on the development of resistance under laboratory conditions showed an increase in LC50 from 2.76 (for unselected F1 generation) to 5.28 mg AI litre−1 (for selected F9 generation), using a selection concentration of 6.4 mg AI litre−1. This suggested a possibility of the development of resistance under field conditions if there were to be extensive and indiscriminate use of B thuringiensis. These findings are discussed in relation to integrated pest management and the mechanisms of resistance in resistance management tactics. © 2000 Society of Chemical Industry

Development of insecticide resistance in Piophila casei (Diptera: Piophilidae) strains selected with low doses of deltamethrin.

Two populations of the cheese skipper, Piophila casei (L.), were sampled. The 1st was from a sheep farm where no chemical was ever applied; the 2nd was present in a ham factory where chemical treatment with pyrethroids was applied in the past against house flies, Musca domestica L., and Dermestid beetles. A substantial difference between their resistance to deltamethrin was observed (LC50 = 11.56 versus 68.08 micrograms/cm2 for females and 1.11 versus 4.20 micrograms/cm2 for males, respectively). Laboratory strains were established from both populations and were selected at constant rates for up to 20 generations (2, 4, and 7.3 ppm for the strains derived from the 1st population and 40 ppm for that selected from the 2nd population). Males and females of both strains showed an increase in LC50 (tested at the 5th and 19th or 10th generation), except when females were selected at the lowest rate (2 ppm). At the end of the trial, slopes of logit regressions were substantially steeper in strains selected at higher rates, suggesting that the effect of the insecticide was to reduce resistance variance. Crosses between unselected and selected strains were done. Results of survival analysis in F1 hybrids were analogous for males and females and were similar in both reciprocal crosses. LC50S were intermediate between those of the parental strains.

Orchard selection for resistance to a synthetic pyrethroid in organophosphate—resistantTyphlodromus pyriin the UK

Organophosphate resistant Typhlodromus pyri were exposed to deltamethrin in replicated orchard plots from 1986–90. Treatments of 6.3, 3.1, 1.7 and 0.8 g active ingredient (ai) ha−1 deltamethrin were applied 14 times over the 5‐year period; a 12.5 g ai ha−1 treatment was discontinued in 1989 after eight applications. Few phytoseiids were found in the plots receiving the two highest rates of deltamethrin. Bioassays at the end of the five‐year period showed a progressive increase in LC50 from the untreated strain (0.40 ppm ai) to the strain that had been exposed to 3.1 g ai ha‐1 1 (1.50 ppm ai) indicating a four‐fold increase in resistance in these selected mites.

Selection Response and Genetics of Parathion Resistance in the Pacific Spider Mite, Tetranychus pacificus

Parathion resistant and parathion susceptible strains of the Pacific spider mite, Tetranychus pacificus McG., were derived from certain field populations and established as laboratory colonies. The two colonies were characterized by dosage-mortality curves for the effect of parathion and also Aramite® (2-( p-tert butylphenoxyl)-1-methylethyl 2-chloroethyl sulfite). One generation selection experiments for parathion resistance and for Aramite resistance were performed on the susceptible colony. The colony responded to both acaricides. The colony responded to selection for parathion resistance by not only an increase in LC-50 but also by producing a population partitioned into susceptible and resistance classes, thus providing evidence for the existence of a major gene for resistance. The latter genetic hypothesis was then tested by performing conventional crosses between the original susceptible and resistant colonies. The results of these crosses produced further strong evidence For a major mendelian dominant with resistance to parathion dominant to susceptibility.