Bystander effect

Degrfeve B, De Clercq E, Balzarini J (1999) Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues. Gene Ther 6 162-170... 

Antiviral Gene Products with a Bystander Effect.283... 

HIV-1 protein virotoxins (Nath 2002), released from infected cells, have direct bystander effects on neighboring gUa and neurons and cause many of the deleterious consequences of HIV-1. Residual viral proteins, including Tat, gpl20 and Vpr,... 

Information on which parasite products might regulate infected muscle cell characteristics is unresolved. Parasite proteins will be the focus of this discussion. This focus results in part from general lack of information on other secreted products/metabolic wastes and their potential influences on the host cell. In addition, arguments for cell-permeable parasite products are less compelling, and no clear evidence exists for a bystander effect in which bona fide infected cell characteristics become established in neighbouring, uninfected host muscle cells. 

Ishii Morita, H., Agbaria, R., Mullan, C.A., Hirano, H., Koeplin, D.A., Ram, Z., Oldfield, E.H., lohns, D.G., and Blaese, R.M., Mechanism of bystander effect killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment, Gene Therapy, 1997, 4, 244—251. 

Bystander effects are also known for a variety of alkychlorocarbenes.60,80,86-88 Absolute rate constants for the rearrangements of MeCCl (15), EtCCl (61), and i-PrCCl (62), as determined by photoacoustic calorimetry were reported by LaV-illa and Goodman.60... 

Ph migration in PhC CCl gives the inherent migratory aptitudes free of bystander effects.80 The 1,2-Ph shift ( a = 9.2 kcal/mol) is preferred to the... 

H shift (11.5 kcal/mol). (However, the unfavorable AS associated with Ph migration lowers the differential AG to about 1.7 kcal/mol.) Bystander effects can thus cause the dominance of 1,2-H shifts observed in experiment.80 With PhCH2CCl, for example, 1,2-H shift is aided by the Ph bystander, but there is no bystander to promote the inherently more favorable 1,2-Ph shift. QMT63 may also accentuate the dominance of 1,2-H over 1,2-Ph shifts the latter would not be expected to benefit from QMT.80... 

Note, from Table 4, that kH for PI1CH2CCI is 6 x 107 s 1, about 3 times greater than kH for PI12CHCCI. This underscores the previously noted nonadditivity of bystander effects on rate constants in going from 10a to 66, the second Ph bystander actually slows the 1,2-H shift. The KGH analysis provides a solution to this conundrum. Steric effects in 66 cause the second Ph to adopt... 

The activation energies for these rearrangements depend on solvent in hydrocarbon, the benzylhalocarbenes exhibit Ea 4-5 kcal/mol,29,36,64,66,102 but these values are reduced to 3.2-3.6 kcal/mol in more polar solvents.66,70,71,92 The minimal Ea is represented by Ph2CHCCl which, in TCE, affords Ea = 1.65 kcal/mol.88 With regard to bystander effects, kH for PI1CH2CCI ( 6 x 107 s-1)36 increases to ( 5 x 108)87 upon a-Me substitution to PhCHMeCCl. Conversely, a-Ph substitution (to Ph2CHCCl) reduces kH to 2.1 x 107 s-1 88 see Section VI.C. 

Radiation-induced genomic instability and bystander effects are now well-established consequences of exposure of living cells to ionizing radiation. Cells not directly traversed by radiation may still exhibit radiation effects. This phenomenon, known as bystander effect, has become a major activity in radiation biology and in some cases has challenged the conventional wisdom. An example is the currently accepted models used for low-dose extrapolation of radiation risks. The currently used models assume that cells in an irradiated population respond individually rather than collectively. If bystander effects have implications for health risks estimates from exposure to ionizing radiation, then the question of whether this is a general phenomenon or solely a characteristic of a particular type of cell and the radiation under test becomes an important issue. 

The bystander effect has been observed for a variety of biological end points such as cell survival [158 159], mutation [160-162], sister chromatid exchanges [163], cell transformation [164,165], micronucleated and apoptosis [166], gene expression [167], and radiation genomic instability [168-170]. 

A single o- or p-methyl substituent has no influence on the rate of cyclization of the singlet tolylnitrene to the favored azirine. ° The methyl group has no bystander effect on benzazirine formation. Cyclization of 2,6-dimethylphenyl or 2,4,6-tri-methylphenylnitrenes necessarily proceeds toward a carbon bearing a substituent. A steric effect raises the barrier to cyclization by 1.5-2.0 kcal/mol, in excellent agreement with the predictions of Karney and Borden. The steric effect extends the lifetime of 2,6-dimethylphenylnitrene at ambient temperature to 13 ns in Freon-113 and of 2,4,6-trimethylphenylnitrene to 8 ns, in the same solvent (Table 11.4). ° ... 

In another study, AAV-mediated delivery of the lacZ gene by direct injection to brain tumors which were induced from human glioma cells in nude mice showed that 30% to 40% of the cells along the needle track expressed b-galactosidase subsequent delivery of the HS V-tk/IL-2 genes to these tumors with AAV and administration of GCV to the animals for 6 days resulted in a 35-fold reduction in the mean volume of tumors compared with controls by a significant contribution from the bystander effect (72). 

It is seen from this table that, at the LD50 level, the nucleus has received about the same dose, irrespective of whether X-rays, 3H-dThd or 125I-concanavalin are used as the source of ionizing radiation, while the membrane has received an immense dose with 125I-concanavalin and very little with 3H-dThd. As expected, the cytoplasm lies in between these two extremes. Yet, irradiation of the cytoplasm (single-ion-beam experiments) is not without an effect. It may cause mutations (Wu et al. 1999) and the formation of products that induce apoptosis in nearby (unirradiated) cells (bystander effect Shao et al. 2004). 

Single charged-particle beam irradiation of single cells has been developed to study various aspects of radiation biology such as the bystander effect. This subject exceeds the scope of this book, and only some reference to this technique is made here (Folkard et al. 1997a,b). 

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