Carcinogenicity Studies

Carcinogenicity studies of organochlorine insecticides viz Dichloro-diphenyl trichloroethane (DDT), technical grade Hexachlorocyclohexane (HCH), Lindane (Gamma HCH) and Indian variety of asbestos were carried out as per UICC protocol. Swiss inbred mice were used for insecticides where as asbestos carcinogenicity was studied in Charles Foster rats. The test chemicals were administered by various routes for periods up to 80 weeks. Along with the carcinogenicity studies, chronic toxicity of above chemicals was assessed by sequential histopathological, histochemical, histoenzymo-logical and biochemical parameters.

Carcinogenicity of DDT

Oral and subcutaneous route of exposure resulted in a significant increase in tumours of lymphoreticular tissue, lungs and liver with highest tumour incidence being observed in the group receiving DDT by subcutaneous injections.

Carcinogenicity of HCH

Technical grade HCH was found to be a more potent carcinogen as compared to DDT. Both male and female animals were susceptible to HCH induced tumours but incidence of liver tumours was more in males and those of lymphoreticular system in females.

Following biological/biochemical changes were found to be useful as early markers of HCH induced hepatocarcinogenesis.

  • Decreased levels of Glucose-6-phosphatase and Fructose 1,6-Diphosphatase were found in neoplastic tissues as compared to normal tissue. The activity of these enzymes was nearly absent in the tumors.
  • Serum protein electrophoresis revealed appearance of specific protein bands at different intervals of time.
  • There was gradual reduction in the levels of faster moving LDH isoenzymes with total absence after formation of liver tumours. These observations were made simultaneously from liver as well serum samples.
  • Histochemically accumulation of iron and glycogen in the pre-cancerous stages was a striking observation.
  • Correlation between body burden and histopathology showed that accumulation of HCH isomers in the liver increased up to two months and then decreased. A second peak was observed again at 6 months of exposure. Precisely at this time the liver tumours appeared. Alpha and Beta HCH peaks coincide with onset of tumours at 6th month.

Carcinogenicity of Lindane

With Lindane (Gamma-hexachlorocyclo-hexane) tumour induction was delayed compared to Technical HCH. Lindane was more toxic in acute exposures but the chronic toxic effect was relatively less, suggesting that its long term use is safer than that of technical HCH.

Carcinogenicity of Asbestos

Lungs of exposed animals by intra tracheal intubation appeared very much enlarged in size.  There was diffuse irregular hyperplalsia of alveolar epithelium and tumours observed were mainly medium sized oat cell carcinoma and adenocarcinoma metastasing in other organs.