MORRIS POLLARD 
1009 
Table IV. — Lesions in Germfree Rats 
Strain 
No. 
Age/ 
months 
Males 
Sex 
Females 
Lesions 
Sprague-Dawley 
1 
8 
1 
Adenofibroma 
of breast 
1 
12 
1 
O 
c 
D 
3 
14 
3 
1 
17 
1 
Fibroma 
2 
18 
2 
6 
19 
2 
4 
2 with pitui- 
20 
6 
15 
tary tumors 
Fischer 
2 
18 
20 
11 
12 
2 
18 
20 
Among 20 germfree Sprague-Dawley rats 
that were killed for examinations, benign aden- 
omas were observed in 3 of them ; but none was 
detected among 20 germfree Fischer rats at age 
11 and 12 months. In these, as in the larger 
sample of germfree Wistar rats, other tissue le- 
sions could not be detected that have been ob- 
served in aging conventional rats, such as 
pneumonia and nephrosis.^^'^^ The absence of 
kidney lesions in the germfree rats has been at- 
tributed to an all- vegetable diet (L-485) on 
which the rats have been fed since 1964.8 Tests 
on urines from individual aged germfree rats 
have revealed protein levels of less than 5 mg%, 
which reflected the healthy functional and 
morphological status of their kidneys, which was 
in sharp contrast to nephrotic tissue changes and 
proteinuria up to 50 mg% in conventional coun- 
terpart rats. Liver xanthine oxidase levels and 
bone marrow mineral components remained at 
high levels in aging germfree rats; whereas 
they drifted down in the tissues of conventional 
counterpart rats.^'^ There is no evidence of mal- 
nourishment in the germfree rats which might 
explain the low incidence of diseases in them. 
The changes observed in the tissues of conven- 
tional rats may reflect a manifestation of preco- 
cious clinical senescence. 
Chronic pneumonia of rats is considered a 
"horizontally-transmitted" infectious disease. It 
has not been observed in germfree rats. The 
lung tissues of germfree rats contain no focal 
accumulations of lymphoid cells in the peri- 
bronchial regions. The gastro-intestinal tracts 
of germfree rats are thin-walled and enlarged, 
and the Peyer's patches are small and relatively 
inactive. The enlarged cecum has had little 
pathogenic effect in Lobund germfree rats. 
The spontaneous diseases of germfree rats 
can be characterized more by those that are ab- 
sent, than present. The number of Wistar rats 
examined in excess of age 20 months, has now 
reached 83. Except for 2 of them, all were killed 
as a means of reducing the size of the colony ; so 
it is not known how long 50 % of them will live, 
nor of what they will die. The 50% survival 
time among the conventional Wistar rats was 
18 months. Two germfree rats have died within 
recent months: one (age 7 months) carried a 
localized fibrosarcoma and the other at age 30 
months had monocytic leukemia. Causes of 
these lesions are unknown. 
DISEASES INDUCED IN GERMFREE RATS 
A broad spectrum of malignant neoplastic le- 
sions have been induced experimentally in 
germfree rats by chemical, physical, and biolog- 
ical agents (Table V).'*^-'"' Except from those 
rats which had been inoculated with Gross leu- 
kemia or Rous sarcoma viruses, no viral agent 
has been recovered from the rats, nor from the 
tumor tissues that they carried. The develop- 
ment of malignant breast carcinomas in the 
germfree rats of 1963 may be diet-related,^^ 
since those which were on diet L485 were free 
of such lesions. The data are no more than 
suggestive. Germfree animals have tolerated 
larger doses of the immunosuppressive and cy- 
totoxic drug, cyclophosphamide, than their con- 
ventional counterparts which usually died of 
secondary infections. ^^'^^ Also, germfree rats 
Table V. — Experimental Induction of Lesions in Germ- 
free Rats 
Agent 
Route 
Lesion induced 
Methylcholanthrene intramuscular fibrosarcoma 52 
7, 12 dimethylbenzanthracene oral mammary carcinoma 
53 
7, 12 dimethylbenzanthracene intraperitoneal myelogenous leukemia 
54 
whole-body mammary carcinoma 
55 
whole-body multiple degenera- 
tive lesions 55 
subcutaneous fibrosarcoma 56 
intraperitoneal lymphatic leukemia 
57 
intraperitoneal fibrosarcoma, 
nephroma, osteoma 
58 
x-irradiation 
x-irradiation 
Rous sarcoma virus 
Gross leukemia virus 
Polyoma virus 
