Parádi, E

Polgár, V

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GENETICALLY DETERMINED TI MO l RS IN DROSOPHILA MH \NO-O ASTE RPARÂDI. E., POLGAR. V.Department o f Genetics, o f the Eötvös Lonind University, Budapest Received on 230' February 1 i>74The research of tumours became an important problem of biology ami medicine in the last few decades. This problem has been intensively investigated in vertebrates (in invertebrates the situation is different in spite o f the fact that also in them noticeable abnormal tissues and cell groups are to be found).Works on abnormal tissue growths in insects apply a most diversi­fied nomenclature which indicates that the two kinds of abnormality are non -  homologous at least in case we consider the characteristics of malignant tumours in vertebrates (i. e. uncoordinated growth, autonomous metabolism, invasive character, changed cell surface)! In tlus sense, according to И a r s h b a r g e r and T a y I о r (1968) no malignant tuim nr exists in insects, although other investigators deny tliis (G a t e f  f  et al 1968).The ontogenesis of insects has special properties characteristic only of them, for instance, except some cell types there is no cell division i n adults wide h results in a disability of t lie malignant cells to multiply. '1 his is c ue of the reasons why tumours lack or infrequently occur in adults. The latter fact seems to be supported by K i n g (1969) who discovered uncontrolled cell division with the reproductive organ mul­tiplying in imaginai age, which resulted in the development of an ova­rian tumour in Drosophila meluncr/astcr.Metamorphosis also puts a stop to tumour development in adults. Imaginai discs and histoblasts in larval age are not functional parts o f the larvae and — when formed — larval tumours disappear at meta­morphosis.On the other hand the absence of dispersion of abnormal tissues may be explained among others by the difference between the circulation of insects and vertebrates as well.Further on the genetically determined abnormal tissues as descri­bed in Drosophila melanogasler will be dealt with. 44 ANNALES — Senio Biologica — Tomus 17.The genetic factors taking part in tumour development are at least partly known. In Drosophila melanoyaster the abnormal growths are of most diverse appearance and also show differences as to their effects.Tumorous head (tu — h)The investigations concerning with the tumorous-head (tu —h) strain of Drosophila connect with the name of G a r <1 n e r (1970).Tumorous head malformations are different in size: they are be­nign. They may appear round the eye and antenna in the form of small protuberances but they may also grow to an amorphous tissue mass occupying a considerable part of the head (Gardner 11)70.). Histologi­cally the tumours are built up of abnormal epiderm il cells. Мэзеп- ehyma cells and/or muscle cells may be present inside the tumours.The mutant larvae have a prolonged larval stage. Larvae inca­pable of pupation were described by K o b e l  and В reti  g e i  (1067) as lethal tumorous larvae (It 1 ). Both the extension of the larval stage, and the absence of pupation are associated with an abnormal hormonal milieu (defect of the juvenile hormone metabolism).According to genetic studies the formation of tumorous head character is controlled by two genes, namely tu—1 and tu — 3. Inc recessive tu—1 is located in the sex chromosome (X), and it has no independent phenotypic influence on the tumorous head trait: tu -  1 is a specific modifier of tu —3. The position of the tu —3 gene is located at the 58 th map unit of the third chromosome. It is a semidominant gene. The phenotype is influenced by a polygenic system of modifier genes.Lethal giant larva (1/2/gl4).Earlier G a t e f f  et al. (19(59) examined the 1/2/gl4 Drosophila mutant. This mutation is a recessive one located at the 2ml map unit of the second chromosome. The homozygous mutant larvae have an invasive neuroblastoma of the larval “ brain“ . According to the auf hois it is a malignant, transplantable and lethal tumour, consequently a real neoplasm in vertebrate sense. The cells of the nerve system lose their organ-specific character, the “ brain" of the larvae grows and the larval structure disintegrates without a differentation of the ima­ginai structure having been started, and as a result, the larva dies (Fig. 1.).The examination of the central nervous complex of the mut ant showed that the lobes of the mutant “brain” became progressively deformed, the different cell types were not localized to specific areas as in the wild-tvpe brain (this complex consists of two brain lobes and a ventral ganglion). (Fig. 2 ,3).Fragments of the third instar mutant brain behave differently than the wild brain fragu^^ts following the implantation as well. The mu-- f| PÁ R Á D ! — POLGARtant brain fragments grew rapidly after the implantation into a female abdomen and invaded the ovarium, midgut, killing tlie host within 0 days. In vivo the fragments o f wild-type continued their growth in the adult host, until finally reaching the size of a fully grown third instar larval brain whose structure was compact and never killed theG E N E T IC A L L Y  D ETER M IN ED  TU M O U RS IN  D RO SO PH ILA 51Fig. 2. Cephalic complex of: A third instar wild-type larva, В mutant larva. 1: eye-antennal disc; 2: brain; 3: ventral ganglion. (From G a t e f f  and S c h n e i  d e r  in a n 1989.)Fig. 1. Third instar mutant (1/2/gl4) and wild-type larvae (From G a t e  f f  and S c h n e i d e r m a n  1989)host. Similar differences can lie seen at the in vivo cultivation of the wild and mutant imaginai disc, too: the fragments of wild-type imaginai discs usually metamorphose with the host larvae and then produce a specific integumentary structure (autotypic tissue — H a d o r n  1966). Similarly to the atelotvpic tissues (H a d o rn  1966) the mutant «lise cells kill the host and never form specific stuctures.4 *5 0  P A R Á D I — P O L G A RKig. 3. Frontul section t hrough tViird instur wild-typ:; und ni ttjuit ( 1 '2.'gl4) bruin (schcni i- t ip). (From G u t e I' Г und S c U π e i d e r m ··. u U»:>9.)Ovarian tumoursK i n g  (1969) studied the ovarian tumour mutant of Drosophila. In the ovary of the animal of tumorous genotype the inhibition of coll division stopped, which resulted in hundreds or thousands of cells in the egg chambers. These flies were sterile. The frequency of occurrence of tumors increased with the age of animals.In the production of a similar phenotypic effect two genes are involved:a) fused ( fu )  (jeneThis gene is localized at 59,5 on the linkage map of the .\ chromo­some and has a recessive pleiotropic effect (it influences the wing veins and embryogenesis). The fu  tumours appear gradually in adult. The fit gene has some alleles which differ from each other in the rate of ovarian tumor formation (fu59< fu1; fu02). Where the fusion of a nor­mal and a tumorous chamber takes place, the tumor cells infiltrate into the normal chamber, in this sense fu  tumor cells are invasive.b) female sterile (fes) jeneThe recessive gene fes was localized at 5 on the linkage map of the 2ud chromosome. The homozygous male is fertile while the female is sterile. The fes gene causes abnormality only in the ovarian and acts earlier in ontogenesis than the fu gene. I he examination of animals of/ «/ / «; fes/fes g e n o ty p e  sh ow ed  th a t  th e  fe s  was e p is ta t ic  to  fu .  K in g  (19(H)) supposes a d im er ic  m ito gen  agen t w h ich  can sh orten  th e  in te r ­phase re su lt in g  in a cce le ra tion  o f  ce ll d iv is io n  an d  b y  th is  red u ction  in ce il v o lu m e  is b rou gh t a b ou t d u rin g  th e  su cces ive  d iv is ion s . A c c o rd in g  to  th e  h ypo th es is  d iv is ion  is in h ib ited  when th e  cell vo lu m e  fa lls  to  th e  c r it ic a l m in im u m  va lu e  (50 μ 3). T h e  o v a r ia n  tu m orou s  m u tan ts  p ro ­duce in s tab le  m ito gen  which  resu lts  in  th e  p ro lo n g a tio n  o f  th e  in te r-  m ito t ic  p er iod  and  thu s th e  ce lls  n e v e r  reach  th e  c r it ic a l m in im u m  vo lu m e  re q u ired  fo r  s to p p in g  fu r th e r  d iv is ion s .Melanotic tumoursMelanotic tumours were found in 55 strains o f Drosophila. They are also called melanotic pseudotumours, melanomas.Depending on the strain, the shape, size, number, location and appearance of the tumours are variable. They may appear as single cell masses or complex bodies free-floating in the hemolymph. In most cases they are connected with the hemolymph colls. In the tumorous strains the plasmatocytes may release from the lymph gland and trans­form into lamelloeytes during early larval life; this tranformation nor­mally occurs at the time of pupation. From this early transformation the conclusion is drawn that the metamorphosis of the hemocytes may be pathological. The next step is the aggregation of the hemolymph cells, and this becomes complete at the end o f the larval period. The aggregates may consist of several cell types. The lamelloeytes are at the surface o f the tumour while inside it there are round or polygonal cells to be found ( R o t t i n  о and К о p a c 1966, Oheleloviteh 1969.).At the later stage of tumour development the cells become pig­mented with melanin; the appearance of pigmentation coincides with the degeneration of the cells. Some authors (R i z к i 1957, R o t -  t i η о and К  о p а с 1966) consider the melanotic tumours a mani­festation of inflammatory or degenerative processes because mitotic formations are not to be found in them and sooner or later the cells lose their ability to function.Others ( O h e l e l o v i t e h  1959, H a r η 1 у 1963) béléivé that a neoplastic process may contribute in melanotic tumour formation. The polygonal neoplastic cells are components of the tumours (these cells derived from the large hemocytes to be found in the tumorous strains). The multiplication of the polygonal cells may be stopped by their encapsulation with the spindle-shaped cells (this process can be generally seen in insects at infection). Thus, two different events should form a melanotic tumour: one of them is a neoplastic process, the other an inflammatory one which is a subsequent reaction to the first process.I he results of these events are the degeneration and melanization of the tumour cells.G E N E T IC A L L Y  D ETER M IN ED  TUM O URS IN D RO SO PH ILA 5 3The tumour genes (tu-genes), primarily responsible for tumour formation are located mainly on the second chromosome and are re­cessive (B a r i g о z z i 1969), still the manifestation of the melanotic tumorous character is controlled by the complex genotype (polygene system). The tu-genes are not allelic in the different tumorous strains, and the different genes determine different incidences and sites of tumours.Also such melanotic mutants are known in which the tumorous character is controlled by a single factor ( B á r i g  о v. v. i and S a r i  G о г 1 a 1968).SummaryThe origin and nature of the tumorous changes in insects are not clear yet, but it is a fact that they do not correspond to vertebrate tumours wich means that the term “ tumour” covers different altera­tions in insects and vertebrates. All this does not mean that insects are incapable of developing true neoplasms or that insect neoplasms sim­uld necessarily present characteristics o f vertebrate neoplasms. A conti­nuously growing number of researchers accept the assumption that for­mation and growth of abnormal cell groups described as tumours in insects result from abnormal cell accumulation, however, not from irre­gular cell division.'flic genetic determinants of certain types of tumours in Drosophila are well known, in case of others, for example in melanotic alterations the whole genom takes part in tumour formation. The fact that in case of melanotic tumours numerous non-allelic genes develop similar phenotypes makes the elucidation of the role of the genetical factors more difficult. A further problem in the examination of insect tumours: the penetrance of tumour-forming genes is greatly influenced by the environmental factors. Progress in studies of insect oncology will pro­bable lead to a situation where the subject of the investigations will not be to search for homology with the vertebrate neoplasms but a more perfect knowledge of the characteristics and inducing factors of insect tumours.REFERENCESB a i· i g <> z ·/ i. C. 1969. Genetic control of melanotic tumors in Drosophila. .Vat. Cancer Inst. Monograph ül: 277 — 291.B a r i g о z. z i, C. — S a r i  G о r 1 a, M. 196S. Chromosomal and extrachromosomal transmission o f cellular melanization in the Freckled phenotype in Drosophila melanogaster. Genet. Iles. 11: 141 — 150.G a rd  пе г ,  E. .1. 1970. Tumorous head in Drosophila. Adv. Genet, lo: 115—147.G a t e f  f. К. — S c h n e i d  e r in a η, Η. Λ. 1969. Neoplasms in mutant and cultured wild-type tissue o f Drosophila. Nat. Cancer Inst. Monograph »1: 365 — 397.54 PARADI — POLGARG h e l e l o v i c h ,  S. 1059. I'm· tumeur héréditaire de la Drosophile (l)rosophila mela· nogaster Meig.). Etude histologique et discussion générale. Biol. Med. (Paris) 48: 52 -  97.G h e l e l o v  i t c h ,  S. 1969. Melanotic tumors in Drosophila melanogasler. Nat. Cancer Inst. Monograph .41: 263 — 277.H a d о r n, E. 1966. Konstanz, Wehsei und Typus der Determination und Differenzierung in Zellen aus männlichen Genitalscheiben von Drosophila melanogasler in Dauerkul­tur. Develop. Biol. 13: 424 — 509.H a r η 1 y. Μ. Η. 1963. Induced hereditary change in Drosophila by injected extracts o f neoplastic flies, mice or humans. Ann. NY. Acad. Sci. 100: 817 — 826.H a r s h b a r g e  r, .1. — T  a у 1 о r, R. L. 1968. Neoplasms o f Insects. Ann. Rev.Entom. 13: 159- 190.K i n g. R. C. 1969. Hereditary ovarian tumors o f Drosophila melanogasler. Nat. Cancer Inst. Monograph 31: 323 — 347.К о b e 1. H. R. — van B r e i i g e  1, F. M. A. 1967. Observations on Iti (lethal tumorous larvae) o f Drosophila melanogasler. Genetica. 38: 305 — 327.R i /. к i, M. T. M. 1957. Tumor formation in relation to metamorphosis in Drosophila melanogasler. J. Morph. 100: 459 — 472.R o t t i n e ,  A. — К  о p a c, M. -J. 1966. Pathogenesis o f spontaneously — occuring and induced melanotic granuloma in Drosophila melanogasler. Prog. Exp. Tumor Res. 8: 66-94.G E N E T IC A L L Y  D ETER M IN ED  TU M O U RS IN  D RO SO PH ILA gg

Genetically determined tumours in Drosophila melanogaster

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Genetically determined tumours in Drosophila melanogaster

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