Evaluation of the mutagenic effects of SV40 in mouse, hamster, and mouse-human hybrid cells

We have examined the ability of SV40 to induce changes in drug or temperature resistance in mouse, hamster, and mouse-human hybrid cells. SV40 induced a substantial increase of cells resistant to 5-bromodeoxyuridine + trifluorothymidine in Balb/c 3T3 cells and induced an increase of hybrid cells resistant to 6-thioguanine. SV40 was found to be nonmutagenic or weakly mutagenic in other test systems. The 3T3 cells were T-antigen positive, exhibited a marked reduction in TK activity, were heterogeneous for [ 3 H]BrdU incorporation by autoradiography, and exhibited instability of the drug-resistance phenotype, suggesting that SV40 may be inducing resistance by an epigenetic process. SV40-induced 6-thioguanine resistance in the hybrids appears to occur predominantly by chromosome loss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45539/1/11188_2005_Article_BF01233058.pd

REGENERATION OF TRANSGENIC PAPAYA (Carica papaya) PLANTS

Stable transformation of papaya (Carica papaya L.) has been achieved following DNA delivery via high velocity microprojectiles. Three types of embryogenic tissues, including immature zygotic embryos, hypocotyl sections, and somatic embryos derived from both, were bombarded with tungsten particles carrying chimeric genes coding for NPT II, GUS, and the coat protein of a mild mutant strain HA 5-1 of papaya ringspot virus. All tissue types were cultured prior to and following particle bombardment on half-strength.MS medium supplemented with 10 mg/1-1 2,4-D, 400 mg/lrI glutamine, and 6% sucrose. Upon transfer to 2,4-D-free medium containing 150 mg/l-1 kanamycin sulfate, 12 isolates regenerated somatic embryos, and five of these produced leafy shoots six to nine months following bombardment. Tissues from 11 isolates were assayed for NPTII activity, and nine were positive. Five out of 12 isolates assayed for GUS expression were positive. Three isolates were positive for both NPTII and GUS

Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivo efficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50's comparable to that of the control treatment pyrimethamine with little to no cytotoxicity. The best of these, KGW44 and KGW59, had higher metabolic stability than KG8. In an in vivo T. gondii murine model, KGW59 significantly increased survivorship. This work provides new insights for optimization of this novel chemotype. Keywords: Toxoplasma gondii, Drug discovery, Lead compounds, Anti-parasitic