DNA SYNTHESIS PART
OF T.
THE I.
IN V A R I O U S INTACT
CELLS
ALBINO
RAT
OF
THE
EXOCRINE
PANCREAS
Polyakova
UDC612.34:612.398.145.1-087.347
A differential count was made of the DNA-synthesizing cells in various p a r t s of the exocrine epithelium of the intact p a n c r e a s of sexually m a t u r e male albino r a t s s a c r i f i c e d 1 h after a single injection of thymidine-H 3. The a c i n a r c e l l s showed low proliferative activity (0.18 • 0.05%). The highest labeling index was found in the epithelium of the ducts. However, the lining m e m b r a n e of the ducts consisted of a h e t e r o m o r p h i c s y s t e m of cells with a varying level of DNA synthesis. The labeling index of the nuclei of the c e n t r o a e i n a r cells was 2.5 times higher than that of the a c i n a r epithelium and amomlted to 0.48 • 0.17 %, whereas the epithelium of the i n t e r c a l a r y ducts had an e x t r e m e l y low labeling index: 0.09 9 0.09 %, c o m pared with 0.27 • 0.09 % for the intralobular ducts and 0.50 • 0.08 % for the interlobular ducts. KEY WORDS: DNA synthesis; p a n c r e a s ; a c i n a r cells; proliferative activity.
The p a n c r e a s is r e g a r d e d as an o r g a n with low proliferative and, consequently, low mitotic activity [4, 5, 7, 10, 12, 15, 16]. The use of thymidine-H 3 showed that the n u m b e r of a c i n a r cells in the phase of DNA synthesis preceding mitosis is s m a l l in the rat and mouse p a n c r e a s , namely 0.1-1.0% [2, 6, 8, 11, 13, 14, 16]. The object of this investigation was to study proliferation of the a c i n a r and c e n t r o a c i n a r cells as well as the cells of the i n t e r c a l a r y , intralobular, and interlobular ducts. EXPERIMENTAL
METHOD
E x p e r i m e n t s were c a r r i e d out on 5 intact male albino r a t s weighing 150-180 g. To study DNA synthesis thymidine-H 3 was used as the DNA p r e c u r s o r and was injected subcutaneously 1 h before s a c r i f i c e in a dose of 0.5 ~tCi/g body weight. To exclude diurnal fluctuations in cell division the animals were killed at the same time of day (10-11 a.m.), the time of maximal mitotic activity in the epithelium of the gland [4, 5], a f t e r starvation for 24 h. P i e c e s of p a n c r e a s were fixed in Bouin's and C a r n o y ' s m i x t u r e s and embedded in paraffin wax: Histoautoradiographs were obtained with the use of type R emulsion after an exposure of 25 days. Sections 5 p in thickness were stained with h e m a t o x y l i n - e o s i n and with gallocyanin by E i n a r s o n ' s method. The n u m b e r of labeled nuclei and the n u m b e r of m i t o s e s were counted in 7000 a c i n a r cells and the mean n u m b e r of c e n t r o a c i n a r cells and cells of the i n t e r c a l a r y , intralobular, and interlobular efferent ducts were calculated per 1000 cells. The labeling index (LI) was e x p r e s s e d in percent and the mitotic coefficient (MC) in promille. The n u m b e r of labeled fibroblasts in the i n t e r a c i n a r c o n n e c t i v e - t i s s u e septa was d e t e r mined fn 100 fields of vision under a magnification of 630 x. The n u m e r i c a l r e s u l t s were subjected to s t a t i s t i c a l analysis. for which P -< 0.05. EXPERIMENTAL The
exocrine
part of the pancreas
has a lobular
Differences were r e g a r d e d as significant
RESULTS structure
and consists
of acini and ducts.
The
Department of Biology with General Genetics and Morphological DeparLment, Central Scientific-Res e a r c h L a b o r a t o r y , Leningrad San.-Gig. Medical Institute. (Presented by Academfcian of the A c a d e m y of Medical Sciences of the USSR S. V. Anichkov.) Translated f r o m Byulleten' ~ k s p e r i m e n t a l ' n o i Biologii i Meditsiny, Vol. ;~8, No. 7, pp. 117-i20, July, 1974. Original article submitted September 25, 1973. 9 1974 Consultants Bureau, a division of Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.
833
TABLE 1. P r o l i f e r a t i v e Activity of Cells of the Exocrine Epithelium Epithelium of acini Rat No.
LI 2 3 4 5
{
MC
0,25 ~ O,5ti 0 0,30 ~0,42 0,I0--+0,08 0,22 ~0,42 0,01 ~ O,{4 0 0,{4 ~0,28
Epithelium of ducts centroacinar intercalary cell LI 0,37 • 0,7 8_+0,44 1,07 -4-0,44
I MC
0,17_+0,01 0
M e a n {0,18~0,05{0,02_+0,01{0,48•
LI 0 0,45 • 0 0 0
0 {0,09_.+0,09
intralobular intcrlobular
{MC
LI
~0
0,.~0,3,
O0 0,65• 0,4 -A-_O,13 0 O, ~_ 0,25
010.27•
{MC
LI 0.,4•
{ MC 0
0,29 • 0,50 0 0,43 -+-0,[9 0 0,64-)-0,31 0 0i42__O,18 0
0 10,50~0,08[ O
Note. LI e x p r e s s e d in percent, MC in~ i n t e r a c i n a r i n t r a l o b u l a r s e p t a c o n s i s t of loose connective tissue in which the n u m b e r of DNA-synthesizing f i b r o b l a s t s counted was 4.2 :~ 0.64 in 100 fields of vision. The acini a r e formed by conical cells with a distinct p o l a r differentiation of t h e i r c y t o p l a s m and they contain one or, l e s s frequently, two nuclei. An i r r e g u l a r di'stribution of labeled nuclei is o b s e r v e d in the epithelium of the acini. As a rule the distribution of DNA-synthesizing c e l l s was focal in c h a r a c t e r . The intensity of thymidine-H 3 incorporation into the epithelium of the acini in albino r a t s showed c o n s i d e r a b l e variation in the individual a n i m a l s (Table 1). The p r e s e n c e of c e n t r o a c i n a r c e l l s within the glandular t e r m i n a l portions is a distinguishing feature of the s t r u c t u r e of the pa~acreas. LI of these c e l l s was 2.5 t i m e s higher than in the a c i n a r epithelium, n a m e l y 0.48 • 0.1'7%. The s e c r e t i o n of the gland is d i s c h a r g e d through a s y s t e m of ducts lined with simple epithelium. The lining of the i n t e r c a l a r y portion c o n s i s t s of simple s q u a m o u s epithelium which, in m o s t a n i m a l s studied, had no labeled nuclei (Table 1). The squamous epithelium of the i n t e r c a l a r y ducts changed into cubical e p i thelium as the duct e n l a r g e d to b e c o m e an i n t r a l o b u l a r duct, and just as in the a c i n a r epithelium, LI showed c o n s i d e r a b l e individual variation, with a m e a n value of 0.27 * 0.09% (Table 1, Fig. la). The i n t e r l o b u l a r ducts lined with c y l i n d r i c a l epithelium had an i n c r e a s e d n u m b e r of DNA-synthesizing cells, on the a v e r a g e 0.50 9 0.08% (Fig. lb). Differential counting of the cell populations in the phase of DNA synthesis a f t e r injection of thymidineH 3 thus showed that the a c i n a r c e l l s have low pro!iferaLive activity (0.18 :~ 0.05%). The epithelium of the ducts had the highest LI. However, the lining of the ducts c o n s i s t s of a h e t e r o m o r p h i e s y s t e m of c e l l s with a ;r level of DNA synthesis, LI f o r the nuclei of the c e n t r o a c i n a r c e l l s was 2,5 t i m e s higher than for
Fig. 1. DNA synthesis in c e l l s of i n t r a l o b u l a r (a) and i n t e r l o b u l a r (b) duct.
834
the epithelium of the acini. A v e r y low LI (0,09 • 0.09%) was found in the i n t e r c a l a r y ducts, c o m p a r e d with 0.27 • 0.09% in the i n t r a l o b u l a r and 0.5 ~0.08 % in the i n t e r l o b u l a r ducts (Fig. 2). Mitoses w e r e found e x t r e m e l y r a r e l y in the s t r u c t u r e s listed above (Table 1).
0,6 0,s
0.3
0.1 0
i 2 3 4 5 Fig. 2. D i a g r a m of inm n s i t y of incorporation of thymidine-H 3 (in p e r cent) in a c i n a r (1) and c e n t r o a c i n a r c e l l s (2) and in i n t e r c a l a r y (3), i n t r a l o b u l a r (4), and int e r l o b u l a r (5) ducts.
It has been shown his~oauteradiographically [16] that, s t a r t i n g f r o m the 30th day of the p o s t e m b r y o n i c period for albino r a t s , the r a t e of DNA s y n t h e s i s in the a c i n a r c e l l s of the p a n c r e a s falls s h a r p l y by c o m p a r i s o n with the e a r l y s t a g e s of p o s t e m b r y o n i c development, as a r e s u l t of a switch during the period of growth to a slow rate of p r o l i f e r a t i o n of the a c i n a r cells, a dec r e a s e in the r a t e of DNA s y n t h e s i s in them, and lengthening of the S, G2, and M phases, In labile t i s s u e s , such as the epithelium of the s m a l l i n t e s tine, in which the rapid f o r m of p r o l i f e r a t i o n o c c u r s , this p r o c e s s is absent. The focal c h a r a c t e r of the distribution of the DNA-synthesizing cells of the acini is evidently explained by their different functional states. No dependence on blood supply could be e s t a b l i s h e d [16]. T h e s e r e s u l t s , obtained in e x p e r i m e n t s on sexually m a t u r e intact r a t s , a g r e e with data in the l i t e r a t u r e on the low p r o l i f e r a t i v e activity of the a c i n a r epithelium and they m a k e good the absence of information in the l i t e r a t u r e on the much higher level of DNA s y n t h e s i s (except in the i n t e r c a l a r y ducts) in the c e l l s of the duct s y s t e m .
The r a t h e r lower level of p r o l i f e r a t i o n in the a n i m a l s investigated than was found by o t h e r w o r k e r s [6, 11] in t h e i r e x p e r i m e n t s was evidently due to the fact that the r a t s s t a r v e d for 24 h. These r e s u l t s shed c o n s i d e r a b l e light on the r e a c t i v e changes in e l e m e n t s of the exocrine p a r t of the p a n c r e a s a f t e r various e x p e r i m e n t a l p r o c e d u r e s : r e s e c t i o n , transplantation, d i s t u r b a n c e of the hormonal balance, etc. LITERATURE 1. 2. 3. 4. 5. 6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16.
CITED
A . A . Voitkevich, R e g e n e r a t i v e P r o c e s s e s and H o r m o n e s [in Russian], Leningrad (1965). I . A . Zelenina, in: Conditions of R e g e n e r a t i o n of Organs and T i s s u e s in A n i m a l s [in Russian], Moscow (1969), p. 89. E . I . Klimova, Trudy G o r ' k o v s k . Med. Inst., 3.2, 231 (1970). I . V . M a r k e l o v a , Byull. ]~ksperim. Biol. i Med., No. 6, 74 (1962). I . V . M a r k e l o v a , R e g e n e r a t i o n and Cell Division in A n i m a l s [in Russian], Moscow (1964), p. 186. I . V . M a r k e l o v a , Tsitologiya, No. 3, 318 (1967). L . N . Moralev, P r o b l e m s in R e g e n e r a t i o n and Cell Division [in Russian], Moscow (1969), p. 23. A . A . P u z y r e v , Effect of Male Sex H o r m o n e s on R e g e n e r a t i o n of the Albino Rat P a n c r e a s , A u t h o r ' s A b s t r a c t of C a n d i d a t e ' s D i s s e r t a t i o n [in Russian], Leningrad (1971). G . G . Samsonidze, M. I. Chichinadze, and K. N. B a r a b a d z e , Trudy. G o r ' k o v s k . Med. Inst., 3_.~2,228 (1970). G, Duff and H. Starr, Proc. Soc. Exp. Biol. (New York), 57, 280 (1944). P. Fitzgerald, K. Vinijachaikul, B. Carol, et al., Am. J. Path., 5__22,1039 (1968), W. Hughes, V. Bond, G. Brecher, et al., Proc. Nat. Acad. Sci. (Washington), 4_~4,476 (1958). B. M e s s i e r and C. Leblond, Am. J. Anat., 10.. 247 (1960). B. Schultze and W. Oehlert, Science, 131.____,737 (1960). J. Shaffer, in: Handbuch d e r m i k r o s c k o p i s c h e n Anatemie des Menschen, VoL 2, Berlin (1927), p. 214. G. Wenzel, E. St6cker, and W. Heine, Arch. Path. Anat., 1__00,118 (1972).
835
OF T.
THE I.
IN V A R I O U S INTACT
CELLS
ALBINO
RAT
OF
THE
EXOCRINE
PANCREAS
Polyakova
UDC612.34:612.398.145.1-087.347
A differential count was made of the DNA-synthesizing cells in various p a r t s of the exocrine epithelium of the intact p a n c r e a s of sexually m a t u r e male albino r a t s s a c r i f i c e d 1 h after a single injection of thymidine-H 3. The a c i n a r c e l l s showed low proliferative activity (0.18 • 0.05%). The highest labeling index was found in the epithelium of the ducts. However, the lining m e m b r a n e of the ducts consisted of a h e t e r o m o r p h i c s y s t e m of cells with a varying level of DNA synthesis. The labeling index of the nuclei of the c e n t r o a e i n a r cells was 2.5 times higher than that of the a c i n a r epithelium and amomlted to 0.48 • 0.17 %, whereas the epithelium of the i n t e r c a l a r y ducts had an e x t r e m e l y low labeling index: 0.09 9 0.09 %, c o m pared with 0.27 • 0.09 % for the intralobular ducts and 0.50 • 0.08 % for the interlobular ducts. KEY WORDS: DNA synthesis; p a n c r e a s ; a c i n a r cells; proliferative activity.
The p a n c r e a s is r e g a r d e d as an o r g a n with low proliferative and, consequently, low mitotic activity [4, 5, 7, 10, 12, 15, 16]. The use of thymidine-H 3 showed that the n u m b e r of a c i n a r cells in the phase of DNA synthesis preceding mitosis is s m a l l in the rat and mouse p a n c r e a s , namely 0.1-1.0% [2, 6, 8, 11, 13, 14, 16]. The object of this investigation was to study proliferation of the a c i n a r and c e n t r o a c i n a r cells as well as the cells of the i n t e r c a l a r y , intralobular, and interlobular ducts. EXPERIMENTAL
METHOD
E x p e r i m e n t s were c a r r i e d out on 5 intact male albino r a t s weighing 150-180 g. To study DNA synthesis thymidine-H 3 was used as the DNA p r e c u r s o r and was injected subcutaneously 1 h before s a c r i f i c e in a dose of 0.5 ~tCi/g body weight. To exclude diurnal fluctuations in cell division the animals were killed at the same time of day (10-11 a.m.), the time of maximal mitotic activity in the epithelium of the gland [4, 5], a f t e r starvation for 24 h. P i e c e s of p a n c r e a s were fixed in Bouin's and C a r n o y ' s m i x t u r e s and embedded in paraffin wax: Histoautoradiographs were obtained with the use of type R emulsion after an exposure of 25 days. Sections 5 p in thickness were stained with h e m a t o x y l i n - e o s i n and with gallocyanin by E i n a r s o n ' s method. The n u m b e r of labeled nuclei and the n u m b e r of m i t o s e s were counted in 7000 a c i n a r cells and the mean n u m b e r of c e n t r o a c i n a r cells and cells of the i n t e r c a l a r y , intralobular, and interlobular efferent ducts were calculated per 1000 cells. The labeling index (LI) was e x p r e s s e d in percent and the mitotic coefficient (MC) in promille. The n u m b e r of labeled fibroblasts in the i n t e r a c i n a r c o n n e c t i v e - t i s s u e septa was d e t e r mined fn 100 fields of vision under a magnification of 630 x. The n u m e r i c a l r e s u l t s were subjected to s t a t i s t i c a l analysis. for which P -< 0.05. EXPERIMENTAL The
exocrine
part of the pancreas
has a lobular
Differences were r e g a r d e d as significant
RESULTS structure
and consists
of acini and ducts.
The
Department of Biology with General Genetics and Morphological DeparLment, Central Scientific-Res e a r c h L a b o r a t o r y , Leningrad San.-Gig. Medical Institute. (Presented by Academfcian of the A c a d e m y of Medical Sciences of the USSR S. V. Anichkov.) Translated f r o m Byulleten' ~ k s p e r i m e n t a l ' n o i Biologii i Meditsiny, Vol. ;~8, No. 7, pp. 117-i20, July, 1974. Original article submitted September 25, 1973. 9 1974 Consultants Bureau, a division of Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.
833
TABLE 1. P r o l i f e r a t i v e Activity of Cells of the Exocrine Epithelium Epithelium of acini Rat No.
LI 2 3 4 5
{
MC
0,25 ~ O,5ti 0 0,30 ~0,42 0,I0--+0,08 0,22 ~0,42 0,01 ~ O,{4 0 0,{4 ~0,28
Epithelium of ducts centroacinar intercalary cell LI 0,37 • 0,7 8_+0,44 1,07 -4-0,44
I MC
0,17_+0,01 0
M e a n {0,18~0,05{0,02_+0,01{0,48•
LI 0 0,45 • 0 0 0
0 {0,09_.+0,09
intralobular intcrlobular
{MC
LI
~0
0,.~0,3,
O0 0,65• 0,4 -A-_O,13 0 O, ~_ 0,25
010.27•
{MC
LI 0.,4•
{ MC 0
0,29 • 0,50 0 0,43 -+-0,[9 0 0,64-)-0,31 0 0i42__O,18 0
0 10,50~0,08[ O
Note. LI e x p r e s s e d in percent, MC in~ i n t e r a c i n a r i n t r a l o b u l a r s e p t a c o n s i s t of loose connective tissue in which the n u m b e r of DNA-synthesizing f i b r o b l a s t s counted was 4.2 :~ 0.64 in 100 fields of vision. The acini a r e formed by conical cells with a distinct p o l a r differentiation of t h e i r c y t o p l a s m and they contain one or, l e s s frequently, two nuclei. An i r r e g u l a r di'stribution of labeled nuclei is o b s e r v e d in the epithelium of the acini. As a rule the distribution of DNA-synthesizing c e l l s was focal in c h a r a c t e r . The intensity of thymidine-H 3 incorporation into the epithelium of the acini in albino r a t s showed c o n s i d e r a b l e variation in the individual a n i m a l s (Table 1). The p r e s e n c e of c e n t r o a c i n a r c e l l s within the glandular t e r m i n a l portions is a distinguishing feature of the s t r u c t u r e of the pa~acreas. LI of these c e l l s was 2.5 t i m e s higher than in the a c i n a r epithelium, n a m e l y 0.48 • 0.1'7%. The s e c r e t i o n of the gland is d i s c h a r g e d through a s y s t e m of ducts lined with simple epithelium. The lining of the i n t e r c a l a r y portion c o n s i s t s of simple s q u a m o u s epithelium which, in m o s t a n i m a l s studied, had no labeled nuclei (Table 1). The squamous epithelium of the i n t e r c a l a r y ducts changed into cubical e p i thelium as the duct e n l a r g e d to b e c o m e an i n t r a l o b u l a r duct, and just as in the a c i n a r epithelium, LI showed c o n s i d e r a b l e individual variation, with a m e a n value of 0.27 * 0.09% (Table 1, Fig. la). The i n t e r l o b u l a r ducts lined with c y l i n d r i c a l epithelium had an i n c r e a s e d n u m b e r of DNA-synthesizing cells, on the a v e r a g e 0.50 9 0.08% (Fig. lb). Differential counting of the cell populations in the phase of DNA synthesis a f t e r injection of thymidineH 3 thus showed that the a c i n a r c e l l s have low pro!iferaLive activity (0.18 :~ 0.05%). The epithelium of the ducts had the highest LI. However, the lining of the ducts c o n s i s t s of a h e t e r o m o r p h i e s y s t e m of c e l l s with a ;r level of DNA synthesis, LI f o r the nuclei of the c e n t r o a c i n a r c e l l s was 2,5 t i m e s higher than for
Fig. 1. DNA synthesis in c e l l s of i n t r a l o b u l a r (a) and i n t e r l o b u l a r (b) duct.
834
the epithelium of the acini. A v e r y low LI (0,09 • 0.09%) was found in the i n t e r c a l a r y ducts, c o m p a r e d with 0.27 • 0.09% in the i n t r a l o b u l a r and 0.5 ~0.08 % in the i n t e r l o b u l a r ducts (Fig. 2). Mitoses w e r e found e x t r e m e l y r a r e l y in the s t r u c t u r e s listed above (Table 1).
0,6 0,s
0.3
0.1 0
i 2 3 4 5 Fig. 2. D i a g r a m of inm n s i t y of incorporation of thymidine-H 3 (in p e r cent) in a c i n a r (1) and c e n t r o a c i n a r c e l l s (2) and in i n t e r c a l a r y (3), i n t r a l o b u l a r (4), and int e r l o b u l a r (5) ducts.
It has been shown his~oauteradiographically [16] that, s t a r t i n g f r o m the 30th day of the p o s t e m b r y o n i c period for albino r a t s , the r a t e of DNA s y n t h e s i s in the a c i n a r c e l l s of the p a n c r e a s falls s h a r p l y by c o m p a r i s o n with the e a r l y s t a g e s of p o s t e m b r y o n i c development, as a r e s u l t of a switch during the period of growth to a slow rate of p r o l i f e r a t i o n of the a c i n a r cells, a dec r e a s e in the r a t e of DNA s y n t h e s i s in them, and lengthening of the S, G2, and M phases, In labile t i s s u e s , such as the epithelium of the s m a l l i n t e s tine, in which the rapid f o r m of p r o l i f e r a t i o n o c c u r s , this p r o c e s s is absent. The focal c h a r a c t e r of the distribution of the DNA-synthesizing cells of the acini is evidently explained by their different functional states. No dependence on blood supply could be e s t a b l i s h e d [16]. T h e s e r e s u l t s , obtained in e x p e r i m e n t s on sexually m a t u r e intact r a t s , a g r e e with data in the l i t e r a t u r e on the low p r o l i f e r a t i v e activity of the a c i n a r epithelium and they m a k e good the absence of information in the l i t e r a t u r e on the much higher level of DNA s y n t h e s i s (except in the i n t e r c a l a r y ducts) in the c e l l s of the duct s y s t e m .
The r a t h e r lower level of p r o l i f e r a t i o n in the a n i m a l s investigated than was found by o t h e r w o r k e r s [6, 11] in t h e i r e x p e r i m e n t s was evidently due to the fact that the r a t s s t a r v e d for 24 h. These r e s u l t s shed c o n s i d e r a b l e light on the r e a c t i v e changes in e l e m e n t s of the exocrine p a r t of the p a n c r e a s a f t e r various e x p e r i m e n t a l p r o c e d u r e s : r e s e c t i o n , transplantation, d i s t u r b a n c e of the hormonal balance, etc. LITERATURE 1. 2. 3. 4. 5. 6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16.
CITED
A . A . Voitkevich, R e g e n e r a t i v e P r o c e s s e s and H o r m o n e s [in Russian], Leningrad (1965). I . A . Zelenina, in: Conditions of R e g e n e r a t i o n of Organs and T i s s u e s in A n i m a l s [in Russian], Moscow (1969), p. 89. E . I . Klimova, Trudy G o r ' k o v s k . Med. Inst., 3.2, 231 (1970). I . V . M a r k e l o v a , Byull. ]~ksperim. Biol. i Med., No. 6, 74 (1962). I . V . M a r k e l o v a , R e g e n e r a t i o n and Cell Division in A n i m a l s [in Russian], Moscow (1964), p. 186. I . V . M a r k e l o v a , Tsitologiya, No. 3, 318 (1967). L . N . Moralev, P r o b l e m s in R e g e n e r a t i o n and Cell Division [in Russian], Moscow (1969), p. 23. A . A . P u z y r e v , Effect of Male Sex H o r m o n e s on R e g e n e r a t i o n of the Albino Rat P a n c r e a s , A u t h o r ' s A b s t r a c t of C a n d i d a t e ' s D i s s e r t a t i o n [in Russian], Leningrad (1971). G . G . Samsonidze, M. I. Chichinadze, and K. N. B a r a b a d z e , Trudy. G o r ' k o v s k . Med. Inst., 3_.~2,228 (1970). G, Duff and H. Starr, Proc. Soc. Exp. Biol. (New York), 57, 280 (1944). P. Fitzgerald, K. Vinijachaikul, B. Carol, et al., Am. J. Path., 5__22,1039 (1968), W. Hughes, V. Bond, G. Brecher, et al., Proc. Nat. Acad. Sci. (Washington), 4_~4,476 (1958). B. M e s s i e r and C. Leblond, Am. J. Anat., 10.. 247 (1960). B. Schultze and W. Oehlert, Science, 131.____,737 (1960). J. Shaffer, in: Handbuch d e r m i k r o s c k o p i s c h e n Anatemie des Menschen, VoL 2, Berlin (1927), p. 214. G. Wenzel, E. St6cker, and W. Heine, Arch. Path. Anat., 1__00,118 (1972).
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