Tobacco Documents Online

T:tir Cot•xc•u. Tcat 1'ui;,u•rO R1:$C,it:cJt-I;.S.A.. l.NQ•. MINDRANIDtAN TD: W. U. GaxY3ner and staff f7m: D. H. Fbrd ! !„" ' < I i ~ July 9; 1980 SUBJDCP: Grant 11B 7NR1. Paul D. Lewis, M.D., Hammersmith Hospital, London, England. "Effects of Zbbacco Alkaloids on Cell Productioa in the Developing Brain." SITE VISI'r on Jime 27, 1980. Dr. Letiais is a full-time neuropathologist at the Hamnersmith Hospital, who has been associated in research with Dr. Rabert Balasz for several years sturiying the effect of various internal and external envirornnental factors on eelll generation within the QQS. Z'his type of radiosutflgraphic stvc3y in oonjtmctioa with biocheni.cal anaflysis of IIM can give an accurate picture of times of arrival and migration of various neuronal cell types and Bow they may be influenced by various hornbnal arr' phamaoologic agents. Such work, however, is very tirne consoning. 7hns, a oonsiderable e.xpenditure of time and effort often occurs before results are obtained (see attached reprint for review of this t.ype of study). Curreatly, resu].ts are beginning to accunulate. Soe attachsd progress report for the early preliminary results. Stunnary as folloas: Animals treated with nicotine for the first 12 days after birth showed no effects in forebrain IxvA level (eell number) or in the level of = labeling. (Notet most cells in forebrain are posbni.totic after birth.) In the cerebellun, tbowevex, there was a 25% greater incorporation of ttiymidine label ir•to WA than in control brains. At this age (12 days), a large number of new neurons would be foaoed in cerebellun (granule cells which then differentiate into mature granule cells, st.ellate and basket ce.lls) . Early indications are that this is associated with a shortening of the S pk~ase of the cell cycle. T,his will be tested. A new developnent emerging in the program relates to sone pilot studies Dr. I,Qwis has wndertakea. Apparently, th}mnidine kinase in brain tissue obtained at autopsy in pa-enatal and early postnatal offspring is still capable of activity for a few hours and will lead to an incorporation of 3H-thymidine into new CNP, if brain slices are incvbated in appropriate media imnediately after death of the infant. Once such nw = is labeled, the rate and level of DNA synthesis may be determined in the brain (biochemical analysis) or in miaronearones by radioautography. Once the teclutique has be,xme routine, Dr. lF-wis plans to oaspare brain tissue sliees obtained fian the (INS of expired offspring frcro snoking and nonsnoking mothexs to deteanine if smoke will have any effect on micmneurogenasis in man. Of course, appropriate data fraa the nothers in relatioas to drink9rig history, etc., will also be necessary. Buciget for Ren__eral. The salary for Mr. Backtouse, who works full-time on the project is relat ve y moderate by British standards today ($14,600) in view of many technicians obtaining about $20,000. Recent inflationary conditions in rnrnr....

liK1116F11Q Englard in cmjianction with rhe wea]viess of the dollar have led to extraordir:ary prices and salaries in Europe. Thus, the amount requested for this project is really veLy niodest in view of the a<nount of wnrk required. Peoamendat3on. Oontinued support through the various aspects of the PrograM• D. H. Fbrd DtII': ek atts.