Factores determinantes del desempeño laboral

The diversity an d unpredictability of this m odel h as p o sed as m an y questions as it has answ ered.

Increasing the incidence of tum o u rs in the colony an d facilitating th eir d ev e lo p m e n t at an earlier age is a m ajor aim. This m ig h t be achieved th ro u g h a n u m b e r of approaches. P relim inary d ata suggests th at dietary m an ip u latio n a n d trea tm e n t w ith carcinogens m a y be effective, a lth o u g h the tu m o u rs are still a risin g a r o u n d 18 m o n th s, th e incidence m ay be rising. R adiation at the tim e of m am m ary glan d d ev e lo p m e n t is also k n o w n to p re d isp o se to m am m ary tu m o u r d e v e lo p m e n t in m ice of ce rtain strain s, in clu d in g BA LB/c mice. C rossing w ith transgenic m ice p ossessing o th er oncogenes, or lacking tu m o u r suppressor genes, m ay predispose to earlier onset of tum ours.

The genetic b ac k g ro u n d is clearly im p o rta n t for the d e v e lo p m e n t of tu m o u rs a n d p lacin g this p a rtic u la r tran sg en e on the FVB b a c k g ro u n d m ay re su lt in tu m o u rs of g re a te r fre q u e n c y a n d e a rlie r o n se t th a n see n o n th e B A L B /c b a c k g ro u n d . A ltern a tiv e ly d irec t m icroinjection of eggs from re cen t g e n e ratio n s of m ice in this colony w ith other m am m ary directed transgenes, to p ro d u c e a bigenic m odel, m ay give fu rth e r inform ation.

It is a p p a re n t th at hom ozygote mice, b re d from the n in th g eneration o n w a rd s co ntinue to d e v e lo p tu m o u rs in a sim ilar p ro p o rtio n of anim als. T here is a su g g e stio n th a t tu m o u r onset m ay be earlier an d m ore frequent. C learly the m o d el p ro v id es a so u n d basis for fu rth e r d ev e lo p m e n t an d this sh o u ld n o w in clu d e careful m o n ito rin g a n d o bservation for tu m o u r d evelopm ent in a non-invasive w ay. This sh o u ld enable earlier detection such th at genetic, epigenetic an d environm ental influences to be defin ed m ore carefully. S equ en tial sam p lin g of m a m m a ry g lan d s in a co h o rt of m ice to look for p r e in v a s iv e le s io n s a n d tu m o u rs a t a n e a rlie r sta g e w o u ld fa c ilita te th is in v e stig a tio n .

T he in cre ased incid en ce of ly m p h o m a s in the IL-7 tre a te d p ro p h y la x is g ro u p is p e r h a p s the m o st u n e x p e c te d fin d in g . F u rth e r in v e stig a tio n of th e effect of IL-7 a d m in is tr a tio n in o th e r tra n s g e n ic m o d e ls, p a r tic u la rly th o se w h ic h d e v e lo p sp o n tan eo u s lym p h o m as is indicated. IL-2 an d IL-7 a p p e a r to be acting in a p aracrin e

C h a p te r Seven_______________________________________________________________________F u tu re S tu d ie s

a n d autocrine fashion on the d evelopm ent of ly m p h o m a an d m ore in fo rm atio n a b o u t th eir effects on the im m une system is required.

T ra n sg e n ic m o d els h av e an im p o rta n t, a n d n o w fu lly e s ta b lish e d , ro le in th e investig atio n of tum origenesis. A lthough this stu d y w as beset w ith som e difficulties - p red o m in a n tly a low incidence and late onset of tum o u rs w e hav e n o w reached a p o in t - at tw elve generations - w here the m odel can be m an ip u lated . The original aim of this thesis - to d eterm in e the feasibility of d ev e lo p in g su ch a m o d el - h as b ee n fulfilled. W ith fu rth e r m a n ip u la tio n , eith er g enetic or ep ig en e tic , an eth ical, re lia b le a n d rep ro d u cib le m odel w hich develops tu m o u rs w ith in a reasonable p e rio d m ay be a c h ie v e d .

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