Robert,
While you're into oncology... please try to find other definitive leads
demonstrating why topoisomerase inhibitors (eg, beta-lapachone; cucurmin..)
seem to drastically reduce carcinogenesis.
Certainly that abstract you quoted is relevant & intruiging... and uh,
turmeric is cheap... you can grow the stuff by the bushel ...and it's GRAS.
alain
-----Original Message-----
From: Robert J. Bradbury <bradbury@aeiveos.com>
To: extropians@extropy.com <extropians@extropy.com>
Date: Wednesday, September 27, 2000 8:41 PM
Subject: MOLBIO: insights into cancer
>Oncogene 2000 Apr 13;19(16):1982-91, Gerbitz A, et al
>"Retinoblastoma susceptibility protein, Rb, possesses multiple BRCT-Ws,
>BRCA1 carboxyl-terminus-related W regions with DNA break-binding activity"
>
>Abstract:
>> The BRCT region, the carboxyl-terminus of BRCA1 (the breast cancer
>> susceptibility gene 1 product), is ubiquitous in several proteins
>> that participate in cell cycle checkpoints and DNA repair. We have
>> previously shown that the BRCT regions of TopBP1 (DNA topoisomerase II
>> binding protein 1) and BRCA1 bound DNA breaks. A BRCT-related region,
>> BRCT-W1, in the retinoblastoma susceptibility gene product (Rb) also
>> could bind DNA fragments, independently of DNA sequences. Five BRCT-W
>> regions were found in the Rb family. All BRCT-Ws of Rb bound DNA
fragments.
>> Electron microscopy and treatment with an exonuclease showed that
>> BRCT-Ws bound double-strand DNA breaks. Since some BRCTs are exceptional
>> common relating elements in tumor suppression, our findings reveal novel
>> aspects of the tumor suppression mechanism.
>
>For those of you that don't speak genome, I'll translate. The bottom
>line is that the BRCA1 gene the Rb (retinoblastoma) tumor suppressor
>genes work by binding to DNA double strand breaks. BRCA1 and Rb are
>found to be mutated in breast and retinal cancers respectively. DNA
>double strand breaks are periodically caused by ionizing radation or
>sometimes oxidative lesions). Presumably this either results in the
>activation of repair mechanisms and/or triggering apoptosis (cell death).
>I believe human cells have a tolerance level of several double strand
>breaks before they decide to commit suicide. Presumably this is because
>if the cells have too many double strand breaks it can't figure out which
>ends are supposed to go back together. One example of what happens when
>you put two chromosomes together improperly is Burkitt's lymphoma, when
>the c-myc on chromosome 8 gets mis-joined into chromosomes 2, 14 or 22 into
>various immunoglobulin genes that are normally "on" in white blood cells.
>The mis-regulated c-myc causes the cells to divide out of control.
>
>Mutations in the BRCA1, Rb or some of the other genes with BRCT regions
>would allow the cells to accumulate double strand breaks and not
>undergo apoptosis. In the face of normally operating rejoining
>mechanisms this is going to turn the genome in that cell into
>a huge jumbled mess. For those of you speaking computerese, imagine
>what would happen if your virtual paging routines put the blocks
>being paged out back into random locations in the paging file.
>
>The human strategy contrasts with that of Deinococcus radiodurans that can
>tolerate hundreds of double strand breaks and seems to be capable
>of properly knitting its genome back together.
>
>Robert
This archive was generated by hypermail 2b29 : Mon Oct 02 2000 - 17:39:18 MDT