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In 1943, Albert Schatz, a tender Rutgers collage Ph. D. pupil, labored on a wartime venture in microbiology professor Selman Waksman’s lab, looking for an antibiotic to struggle infections at the entrance strains and at domestic. In his 11th test on a typical bacterium present in farmyard soil, Schatz came across streptomycin, the 1st potent treatment for tuberculosis, one of many world’s deadliest ailments.
As director of Schatz’s examine, Waksman took credits for the invention, belittled Schatz’s paintings, and secretly enriched himself with royalties from the streptomycin patent filed via the pharmaceutical corporation Merck. In an unparalleled lawsuit, younger Schatz sued Waksman, and was once offered the identify of “co-discoverer” and a proportion of the royalties. yet years later, Professor Waksman by myself used to be provided the Nobel Prize. Schatz disappeared into educational obscurity.
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Extra info for Annual Review of Pharmacology and Toxicology Volume 45, 2005 (Annual Review of Pharmacology and Toxicology)
This system allows the detection of HAA mutagenicity by recombinant human P450 without a need for rat liver fractions. These bacteria have also been genetically engineered to express S. typhimurium NAT, and the DNA nucleotide excision repair system has been inactivated (UvrABC) to improve the sensitivity (74, 77, 78). S. typhimurium tester strains have also been used to express human P450s that activate arylamines and HAAs (73, 79, 80). The E. coli strains overexpressing P450s and NAT have been used to characterize P450 1A2 allelic and random variants (81–84).
45:27-49. org by Universitaet Heidelberg on 10/01/05. For personal use only. sgm LaTeX2e(2002/01/18) P1: GCE GUENGERICH bind covalently to DNA. At least four enzyme systems are known to be involved in this secondary activation step in mammals: N-acetyltransferase (NAT), sulfotransferase, prolyl tRNA synthetase, and kinases, yielding reactive N-acetoxy, N-sulfonyloxy, N-prolyloxy, and N-phosphatyl esters, respectively (40–43). The N-hydroxy HAAs can react directly with DNA (32), but the reaction is facilitated when reactive ester derivatives undergo heterocyclic cleavage to yield reactive aryl nitrenium ion species, which preferentially react to form DNA adducts (Figure 2).
20:46–84 Sugimura T. 1985. Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res. 150:33–41 Kato T, Ohgaki H, Hasegawa H, Sato S, Takayama S, et al. 1988. Carcinogenicity in rats of a mutagenic compound, 2amino-3,8-dimethylimidazo[4,5-f ]quinoxaline. Carcinogenesis 9:71–73 Nagao M, Sugimura T. 1993. Carcinogenic factors in food with relevance to colon cancer development. Mutat. Res. 290:43–51 Mueller GC, Miller JA. 1948. The metabolism of 4-dimethylaminoazobenzene by rat liver homogenates.