VPP 211: General Veterinary Pathology (1+1)

CAUSES / ETIOLOGY OF NEOPLASMS

Predisposing causes	Definite causes
Hereditary Breed Age colour Hormones	Physical  Chemical  Biological

 

Predispoing causes

Hereditary

• Hereditary predisposition is observed for some tumours.
• Certain strains of mice are highly susceptible to mammary and liver tumours. e.g. C3H. This is due to simple recessive Mendelian factor.
  • Human e.g. - Neuroblastoma, retinoblastoma and colon, ovarian, prostate, mammary and uterine cancer.
  • Lymphoid leucosis in poultry

Age

The period of life at which cancer appears is called cancer age. The malignant tumours usually occur in old age.

Species	Cancer age
Dog	5 years
Cattle	8-10 years
Human	50 years

• Older age
  • This may be attributed to exposure to carcinogen and accumulation of somatic mutations. Epithelial neoplasms are common in old age. However some tumour occurs at young age. e.g. sarcomas
  • Congenital e.g. nephroblastoma

Colour (Pigmentation)

• Melanin pigment produced by melanocyte protects skin against UV rays of sun. Hence, lack of pigmentation may lead to occurrence of tumours.
• eg. Grey and white horses - malignant melanoma (especially old age); Hereford cattle - ocular squamous cell carcinoma

Hormones

• Hormones like estrogen and progesterone may play a role to predispose animals to cancer. e.g. Estrogen - Mammary tumour, ovarian carcinoma. Progesterone - Mammary tumour in dogs ans cats.

Mammary tumour - Dog - Primary tumour

Definite causes

Physical

• Solar radiation- cutaneous tumours
• It is associated with areas where sunlight is intense, light skinned animals and exposure of the area.
• UV radiation (UVB 280-320 nm) causes pyrimidine dimers injuring DNA causing mutation and tumours.
• Xeroderma pigmentosum - a genetic disease of human in which enzymes required for DNA repair are lacking, hence exposure to UV ray of sunlight results in dry pigmented skin. Whole body radiation can cause leukaemia
• Radiation includes elctromagnetic radiation (UV rays, X rays and gamma radiation and particulate radiation (α, β, proton and neutrons) which are carcinogens.
• X ray - skin tumour
• I¹³¹ - thyroid adenoma
• Radium - osteosarcoma and leukaemia (painters of watches and clocks)

Chemicals

Sir Percival Pott (1775) was the first scientist to identify chemical agent to cause of cancer. In 1915, Yamagiwa and Itchikawa produced cancer in rabbit ears with repeated application of coal tar i.e. experimental carcinogenesis. Kenneway and Cook purified the carcinogen 3, 4 - benzapyrene from crude tar. Other potent chemical carcinogens are benzanthracene, methylcholanthracene (Chlorinated hydrocarbons).

Examples of major chemical carcinogens

• Direct acting
  • Alkylating agents - β propiolactone, Dimethylsulfoxide
  • Aceylating agents - 1 acetyl imidasone
• Indirect acting or procarcinogen - It requires metabolic conversion to become ultimate carcinogen to induce cancer.
  • Polycyclic and heterocyclic hydrocarbons - benzanthracene
  • Nitrosoamines and nitrosoamides - vinyl chloride, aldrin, dieldrin

Mechanism of chemical carcinogenesis

Initiation promotion model

S.No.	Initiator	Promoter	Tumour produced
1	Aflatoxin B1	Methyl sterculate	Hepatocellular carcinoma in trout
2	Benzapyrene	Croton oil	Squamous cell carcinoma inn mouse skin

Biological causes

• Bacteria: Helicobacter pylori – gastric cancer and lymphoma in man; Helicobacter hepaticus – hepatocellular carcinoma in mice
• Parasites
  • Spirocera lupi - Oesophageal fibrosarcoma and osteosarcoma in dogs
  • Cysticercus fasciolaris – fibrosarcoma in rat liver
  • Eimeria stiedae – bile duct tumour in rabbits
  • Schistosoma haematobium – bladder cancer in man
• Viruses
  • DNA viruses – Papova, Shope papilloma, canine oral papilloma, bovine papilloma, human papilloma
    • Pox viruses – fibroma, myxoma in rabbit
    • Herpes virus – Marek’s disease chicken
  • Oncogenic RNA viruses
    • Retroviruses – Lymphoid leucosis
    • Rous sarcoma virus – Tumours in poultry

Ellerman and Bang (1908) were the first to demonstrate viral carcinogenesis and later by Rous. Peyton Rous (1910) produced similar results with fowl sarcomas. Gross (1953) induced leukaemia with cell free filtrate in mice.