A hereditary form of lymphosarcoma in Large White
pigs, associated with an autosomal recessive gene, is
diagnosed usually before 3 months of age and is fatal
by 15 months. The suitability of this condition for
testing anticancer chemotherapeutic agents has been investigated using four agents representing each of the
four major modes of action. Prednisolone, adriamycin
(doxorubicin), cyclophosphamide and cytarabine as single
agents were administered to normal pigs to determine
appropriate dose levels and then to lymphosarcoma cases,
and the results compared with previously reported effects
in man and other species.
Prednisolone produced a reduction in numbers of circulating lymphocytes and in size of lymph nodes, which
was striking in the lymphosarcomatous pigs, an increase
in serum albumin and decrease in serum globulins and involution of the thymus with "overshoot" on recovery.
The lymphosarcoma cases showed improvements in appetite
and vigour and in neutrophil, thrombocyte and red cell
Adriamycin was cumulatively toxic at high
dose levels, producing bone marrow depression, involving
all types of white blood cells, red cells and thrombocytes, gastro-intestinal damage, stunting of growth, alopecia, stomatitis, sclerosis of blood vessels and possibly cardiotoxicity . Lymphosarcoma cases did not survive a dose level of 2mg/kg. One of these
died of liver failure. A dose-level of 1mg/kg produced a general improvement in fitness, body condition
and weight gain with temporary suppression of the tumour
after each dose.
Cyclophosphamide produced few effects, other than
a consistent reversible, neutropenia during the 1st week
after dosing, even at high dose-levels. Alopecia and
haemorrhagic cystitis were not seen. Depression of
skin delayed hypersensitivity response and thymus involution were unexpected results. Lymphosarcoma
cases showed evidence of temporary suppression of the
tumour after each dose.
Normal pigs given cytarabine showed slight weight
loss and progressive bone marrow depression. Antitumour
effect was disappointing, only one lymphosarcomatous
animal showing evidence of response, despite the
fact that levels of deoxycytidine kinase, which activates cytarabine, were shown to be four times higher
in lymphoid tissue from the lymphosarcoma cases compared
with the normal pigs.
Further studies were an investigation of the chemotactic
response to casein of blood monocytes and neutrophils from normal pigs and lymphosarcoma cases, both
untreated and treated with prednisolone.