Genetic differences

Observed differences between strains of rats and mice, as described below, may be the result of gene polymorphisms. In cases involving insecticide selection pressure, resistant populations may arise as a result of direct mutations of insecticide-metabolizing enzymes and/or insecticide target sites that are passed on to succeeding generations. 

In vivo Toxicity. The toxicity of organic compounds has been found to vary between different strains of laboratory animals. For example, mouse strain C3H is resistant to histamine, the LD50 being 1523 mg/kg in C3H/Jax mice as compared with 230 in Swiss/ICR mice that is, the animals of the former strain are 6.6 times less susceptible to the effects of histamine. Striking differences in the toxicity of thiourea, a compound used in the treatment of hyperthyroidism, are seen in different strains of the Norway rat. Harvard rats were 11 times more resistant, and wild Norway rats were 335 times more resistant than were rats of the Hopkins strain. 

The development of strains resistant to insecticides is an extremely widespread phenomenon that is known to have occurred in more than 200 species of insects and mites, and resistance of up to several 100-fold has been noted. The different biochemical and genetic factors involved have been studied extensively and well characterized. Relatively few vertebrate species are known to have developed pesticide resistance and the level of resistance in vertebrates is low compared to that often found in insects. Susceptible and resistant strains of pine voles exhibit a 7.4-fold difference in endrin toxicity. Similarly pine mice of a strain resistant to endrin were reported to be 12-fold more tolerant than a susceptible strain. Other examples include the occurrence of organochlorine insecticide-resistant and susceptible strains of mosquito fish, and resistance to Belladonna in certain rabbit strains. 

Many other significant polymorphisms in xenobiotic metabolizing enzymes have been described, including those for several CYP genes, alcohol and aldehyde dehydrogenases, epoxide hydrolase, and paraoxonase. One interesting polymorphism affecting 

Metabolite Production. Strain variations to hexobarbital are often dependant on its degradation rate. For example, male mice of the AL/N strain are long sleepers, and this trait is correlated with slow inactivation of the drug. The reverse is true in CFW/N mice, which have short sleeping time due to rapid hexobarbital oxidation. This close relationship is further evidenced by the fact that the level of brain hexobarbital at awakening is essentially the same in all stains. Similar strain differences have been reported for zoxazolamine paralysis in mice. 

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R. E. Kouri, Genetic Differences in Chemical Carcinogenesis CRC Press Inc., West Palm Beach, Fla., 1980. 

PO performs vitally important functions in the plant cell and is mainly associated with the oxidation of phenolic compounds and with the formation and strengthening of the cell wall (Passardi et al., 2004). PO is involved in the oxidative transformation of molecules in growth-regulating or signalling activities and - as a result - can also perform regulatory functions in the cell. Plant POs are represented by genetically different proteins with the same enzymatic activity (Welinder et al., 2002). 

It is thus easy to understand why interpretations have also been varied. There needs to be a more systematic approach in our studies, paying more attention to genetic differences that exist and including observations of what happens when stress is released. More teamwork may be needed to apply the range of techniques now at hand. 

Kaundun, S. S., Fady, B., and Lebreton, P. 1997. Genetic differences between Pinus halepensis, Pinus brutia and Pinus e/danca based on needle flavonoids. Biochem. Syst. Ecol. 25 553-562. 

S. Tagaki, Mechanism of iron uptake regulation in roots and genetic differences. Agriculture, Soil Science and Plant Nutrition in the Northern Part of Japan. (Japanese Society of Soil Science and Plant Nutrition eds.), 1984, Tokyo, Japan, p. 190. 

Quetiapine is predominantly metabolized by CYP3A4. Environmental rather than genetic differences are most likely to explain unusual differences in the serum concentration to dose ratio for this antipsychotic (de Leon etal, 2005b). 

These population changes have important implications for pharmacotherapy. It is now widely accepted that genetic differences between the various ethnic groups are quite small and probably less than individual differences. The recent experience with the newly approved congestive heart failure medication, BiDil, suggests that even minor differences can have significant pharmacological consequences. 

Levels of ACHE and PCHE vary in healthy people because of genetic differences or under specific physio-pathological conditions inter-individual coefficients of variation of cholinesterase activity have been determined to be about 15 to 25% for PCHE and 10 to 18% for RBC-ACHE. Corresponding figures for intra-individual variations are 6% and 3 to 7%, respectively (Dillon and Ho, 1987). 

Mating animals that display a required trait and selecting offspring that also display the trait reveals genetic differences in behavioral responses such as cognition. Rats have been selectively bred for high or low emotionality on the basis of defecation rates and these two strains have been found to differ in their sensitivity to the stimulant/depressant effects of nicotine [49]. 

Gonzalez FJ, Nebert DW. Evolution of the P450 gene superfamily animal-plant warfare , molecular drive, and human genetic differences in dmg oxidation. Trends Genet 1990 6 182-186. 

Ensuring Equity Regarding Drugs Based on Genetic Difference... 

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