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The oncogenic activity of the polyoma virus in thymectomized rats
Life Sciences lfo . United States .
7, pp " ~75-~TS, 1963 "
PerB,eson Press,
Inc. Printed is !5e
T1~ OI~COQ~II~IC AC'PIVIT7C OAF TSE POLYOMA VIRUS Ilk
RAT3
M. Vandeputte, P. Dengs, Jr ., R . Legten snd P. De 3o®er Rege Institute,
University of Louvaia, Helgiua
(Received 3 June 1963)
1 . Introduction Polyoma tumors induced in rate seem to contain a new cellular antigen foreign to the normal tissues of the rat ( Vandeputte and De Somer ) . This might explain the resistance to the oncogenic activity of the polyoma virus in rats inoculated with the virus after the neonatal period . As thymectomy at birth is associated with serious impairment of the immunological response to foreign cellular antigens ( Miller, 1962 ), its influence was investigated on the tumor incidence and on the period of time following birth during which the rat remains susceptible to the oncogenic activity of the polyoma virus .
2 . Materiale and Methode Rate ( Albino R strain ) were thymectomized within the first eighteen hours after birth. Approximatively half of the litters were sham-operated . The polyoma virus was injected subcutaneously either immediately after thymectomy or sham-operation or two to three weeks afterwards . In the first case the litters were injected with 0 .05 ml virus ( 10 7 TGID 50 ) . In this experiment a group consisting of nonoperated but neonatally injected rate was also included . In the second case one ~+75
ONCOGEAIC ACTIVITY OF Tl~ POLYOWI VIRUS
476
No .
group of rats was injected with a high dosage of polyoma virus ( 10 8 TCID 50 ) and another with a low dosage ( 2 x 10 4 TCID 50 ) . All animals were kept under observation for three months . At the end of this period they were bled and the organs removed for histological examination . Animals that became sick before the end of the experiment were treated in the same way . The sera were heated at 56 ° C for half an hour and the titer of hemagglutination-inhibiting ( H .I . ) antibodies determined .
3 . Results As indicated in Table 1 the percentage of tumors developing in the rats thymectomized and inoculated at birth was much higher than in the sham-operated and nonoperated control groups . No histological differences were seen between the tumors found in the three groups . High H .I . antibody titers ( 1/4 . 000 to 1/32 .000 ) were found in virtually all tumor-bearing rats . No difference in titer was recorded between the thymectomized and the control rata . TA BLE 1
Polyoma Tumor Incidence in Neonatally inoculated Rats
No .
No . and with inoculated tumors
Tumor type
~fo
Kidney Sarcoma
LipoSarcoma
OsteoSarcoma
Thymect .
21
18(86 ~/°)
18
2
1
Sham-oper .
14
3(21 °j°)
3
0
0
Nonoper .
42
13(25 °f°)
12
1
0
A s shown in Tablet, seven out of 28 rats thymectomized at
7
No . 7
OdFCO®IC AGTIVITY QF TJ~ POLYOl6A VIItUS
477
birth and inoculated subcutaneously two to three weeks afterwards with a high dosage ( lO 8 TGID 50 ) of polyoma virus developed polyoma tumors . All these tumors were cerebral hemangiomas ; none was of the type commonly encountered in rate injected neonatally . Two cerebral hemangiomas were detected eight weeks after the virus inoculation, two after ten weeks, and three at the end of the experiment ( three months after the inoculation of the polyoma virus ) . In two cases positive H .I . antibody titers were recorded ( 1/512, 1/256 ), whereas in the other tumor-bearing and normal rate, no antibodies were found ( 1/32 or less ) . In the control group no polyoma tumors were found . TA BLE 2 Polyoma Tumor Incidence in Rats inoculated at the Age of Two to Three Weeks
No .
No, and with inoculated tumors
Tumor type
°Jo
Kidney Sarcoma
Lipo~ Sarcoma
Cerebral Hemangioma
Thymect . lO 8 TGID 50
28
virus 2x10 4 TGID 50 virus
7(25 %)
0
0
7
32
0
0
0
0
26
0
0
0
0
Sham-oper . 10 8TGID 50 virus
4. Discussion and Conclusion Rata thymectomized at birth seem to be much more sensitive to the oncogenic action of the polyoma virus than are normal or sham .. operated rats . This higher sensitivity is shown in the higher percentage
4~8
O~iCOCiIIfIC ACMVITY QF 7~ POLYO~MA VIfiUS
No . 7
of tumors developing in these thymectomized animals and in a prolongation of the neonatal period during which the animal remains susceptible to the oncogenic activity of the virus, The high antibody titers found in thymectomized rate seem to .indicate that this enhanced sensitivity could be due to an impairment of the immunologic response against foreign cellular antigens contained in the polyoma tumor rather than to a depression of the humoral immunity, Experiments are actually designed to check this possibility, The fact that thymectomized rats inoculated with polyoma virus when two to three weeks old developed only cerebral hemangiomas might also indicate that the immunologic response is not completely depressed and that the tumors can develôp only in an immunologically poorly reacting environment such as the brain.
5 . References 1 . Miller J.F .A .P Ann, N. Y . Acad, Sci . 99, 340 ( 1962 ) . 2 . Vandeputte M, and De Somer P . , Nature, in press,
7, pp " ~75-~TS, 1963 "
PerB,eson Press,
Inc. Printed is !5e
T1~ OI~COQ~II~IC AC'PIVIT7C OAF TSE POLYOMA VIRUS Ilk
RAT3
M. Vandeputte, P. Dengs, Jr ., R . Legten snd P. De 3o®er Rege Institute,
University of Louvaia, Helgiua
(Received 3 June 1963)
1 . Introduction Polyoma tumors induced in rate seem to contain a new cellular antigen foreign to the normal tissues of the rat ( Vandeputte and De Somer ) . This might explain the resistance to the oncogenic activity of the polyoma virus in rats inoculated with the virus after the neonatal period . As thymectomy at birth is associated with serious impairment of the immunological response to foreign cellular antigens ( Miller, 1962 ), its influence was investigated on the tumor incidence and on the period of time following birth during which the rat remains susceptible to the oncogenic activity of the polyoma virus .
2 . Materiale and Methode Rate ( Albino R strain ) were thymectomized within the first eighteen hours after birth. Approximatively half of the litters were sham-operated . The polyoma virus was injected subcutaneously either immediately after thymectomy or sham-operation or two to three weeks afterwards . In the first case the litters were injected with 0 .05 ml virus ( 10 7 TGID 50 ) . In this experiment a group consisting of nonoperated but neonatally injected rate was also included . In the second case one ~+75
ONCOGEAIC ACTIVITY OF Tl~ POLYOWI VIRUS
476
No .
group of rats was injected with a high dosage of polyoma virus ( 10 8 TCID 50 ) and another with a low dosage ( 2 x 10 4 TCID 50 ) . All animals were kept under observation for three months . At the end of this period they were bled and the organs removed for histological examination . Animals that became sick before the end of the experiment were treated in the same way . The sera were heated at 56 ° C for half an hour and the titer of hemagglutination-inhibiting ( H .I . ) antibodies determined .
3 . Results As indicated in Table 1 the percentage of tumors developing in the rats thymectomized and inoculated at birth was much higher than in the sham-operated and nonoperated control groups . No histological differences were seen between the tumors found in the three groups . High H .I . antibody titers ( 1/4 . 000 to 1/32 .000 ) were found in virtually all tumor-bearing rats . No difference in titer was recorded between the thymectomized and the control rata . TA BLE 1
Polyoma Tumor Incidence in Neonatally inoculated Rats
No .
No . and with inoculated tumors
Tumor type
~fo
Kidney Sarcoma
LipoSarcoma
OsteoSarcoma
Thymect .
21
18(86 ~/°)
18
2
1
Sham-oper .
14
3(21 °j°)
3
0
0
Nonoper .
42
13(25 °f°)
12
1
0
A s shown in Tablet, seven out of 28 rats thymectomized at
7
No . 7
OdFCO®IC AGTIVITY QF TJ~ POLYOl6A VIItUS
477
birth and inoculated subcutaneously two to three weeks afterwards with a high dosage ( lO 8 TGID 50 ) of polyoma virus developed polyoma tumors . All these tumors were cerebral hemangiomas ; none was of the type commonly encountered in rate injected neonatally . Two cerebral hemangiomas were detected eight weeks after the virus inoculation, two after ten weeks, and three at the end of the experiment ( three months after the inoculation of the polyoma virus ) . In two cases positive H .I . antibody titers were recorded ( 1/512, 1/256 ), whereas in the other tumor-bearing and normal rate, no antibodies were found ( 1/32 or less ) . In the control group no polyoma tumors were found . TA BLE 2 Polyoma Tumor Incidence in Rats inoculated at the Age of Two to Three Weeks
No .
No, and with inoculated tumors
Tumor type
°Jo
Kidney Sarcoma
Lipo~ Sarcoma
Cerebral Hemangioma
Thymect . lO 8 TGID 50
28
virus 2x10 4 TGID 50 virus
7(25 %)
0
0
7
32
0
0
0
0
26
0
0
0
0
Sham-oper . 10 8TGID 50 virus
4. Discussion and Conclusion Rata thymectomized at birth seem to be much more sensitive to the oncogenic action of the polyoma virus than are normal or sham .. operated rats . This higher sensitivity is shown in the higher percentage
4~8
O~iCOCiIIfIC ACMVITY QF 7~ POLYO~MA VIfiUS
No . 7
of tumors developing in these thymectomized animals and in a prolongation of the neonatal period during which the animal remains susceptible to the oncogenic activity of the virus, The high antibody titers found in thymectomized rate seem to .indicate that this enhanced sensitivity could be due to an impairment of the immunologic response against foreign cellular antigens contained in the polyoma tumor rather than to a depression of the humoral immunity, Experiments are actually designed to check this possibility, The fact that thymectomized rats inoculated with polyoma virus when two to three weeks old developed only cerebral hemangiomas might also indicate that the immunologic response is not completely depressed and that the tumors can develôp only in an immunologically poorly reacting environment such as the brain.
5 . References 1 . Miller J.F .A .P Ann, N. Y . Acad, Sci . 99, 340 ( 1962 ) . 2 . Vandeputte M, and De Somer P . , Nature, in press,