Of tobacco and cancer

T.S. SUBRAMANIAN

DR. A.N. BHISEY, Director of the Cancer Research Institute (CRI), Tata Memorial Centre, is a keen student of cancer, especially cancer caused by tobacco use. The CRI has done significant work in major areas of cancer research, including on how the use of tobacco leads to cancer of the head and the neck (cheeks, tongue and throat) and to what extent workers in the tobacco industry face the risk of contracting cancer.

Dr. Bhisey, who has a Ph.D. in cell biology from Mumbai University, said: "We work on problems relevant to India. Our major thrust area is research on cancer of the head and the neck, which is the number one type of cancer in India." Thus, according to h im, research at the CRI is directed towards oral and throat cancer, which are caused by the chewing of tobacco, smoking and using tobacco in the form of snuff. He said: "We have done a lot of epidemiological studies on this. A major problem is that peopl e stuff tobacco in their mouths and this leads to cancer in the cheeks. This type of cancer is prevalent only in India. However, cancer of the tongue is prevalent in other countries as well."

paan masala

In the case of people who chew tobacco, first a white patch appears on the inside of the cheek. In some people it might lead to cancer. Dr. Bhisey said: "Our inquiry is into the changes that take place when the white patch occurs. The question is, what a re the changes that progressively occur in the cheeks when they come into contact with tobacco? Why do they develop tumours? So we analyse the chemistry of tobacco also."

There are two groups of genes, called oncogenes and suppressor genes. Oncogenes are part of normal genes. In the case of human cancer, several oncogenes get altered in a sequence. The proteins that the genes make get altered. Besides, tobacco-induced can cers, although initially localised, invade the surrounding parts subsequently. This means that cancerous cells become more aggressive. Dr. Bhisey said: "We study the cells that get altered in the pre-cancerous, white-patch stage, and also the progressive stages that lead to the formation of a tumour."

The second group of genes consist of suppressor genes, which maintain tight control on the cell. If their function is impeded, malignancy occurs. The CRI Director said that if one knew the protein that altered the structure of the genes, it would help in understanding cancer. So it was important to understand the changes that occurred in the genes. He added: "Once you see the stages (of changes) and their progress, you can use them to predict whether they will develop into cancer or stay put. All this i nformation can be used to devise strategies for treatment. The information can be used to design drugs that will specifically react with the altered proteins." Dr. Bhisey said that an "interesting" study by CRI scientists had revealed that people who swa llowed tobacco juice faced a high probability of developing stomach cancer.

Five years ago the Government of India asked the CRI to find out whether the use of paan masala which did not have tobacco as an ingredient led to cancer. Dr. Bhisey said: "We did various types of experiments using mice of different strains. The importan t finding of these is that chewing paan masala that does not contain tobacco is also dangerous and those who used it ran the risk of getting cancer. It caused different types of tumours."

In the human body, there are different types of blood cells called lymphocytes. They are involved in killing cancer cells. At the CRI, studies were conducted on how to make this process of killing more efficient. These experiments could not be done on pa tients; the patients' lymphocytes were added to cultured tumourous cells and then it was studied whether the killing of the cancer cells by lymphocytes could be made more efficient. Besides, these tumours were grown in nude mice, which have a very defici ent immune system, and a variety of experiments were carried out.

The CRI analysed tobacco grown in different States, such as Assam, Gujarat and Andhra Pradesh, to find out whether there were 'safer' varieties of tobacco. Tobacco samples were analysed to find out their harmful constituents. The CRI also monitored worke rs in tobacco-related industries for any effect of tobacco on them. Excessively high levels of tobacco dust were found on the factory premises. Chronic inhalation of tobacco dust was found to be associated with increased chromosomal damage in the workers . According to Dr. Bhisey, the study shows that the workers face a greater risk of developing tobacco-related cancers.

Another area studied was whether genetic factors played a role in the susceptibility to tobacco-related cancers. Dr. Bhisey predicted that as the secrets of the human genome unfolded, new medicines would emerge. He said that by looking at individuals' ge netic makeup it might be possible to predict the relative risk to a host of disorders, including cancer. Molecular genetics will, therefore, dominate the scene, according to him. "With this in mind, considerable emphasis is placed at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC, in Navi Mumbai, where the CRI will shift soon) on developing recombinant DNA (deoxyribonucleic acid) technology, molecular and cellular immunology, molecular genetics and molecular epidemiology," t he CRI Director said.

AT the CRI, important research on gene therapy is under way. It is the first institute in India to have initiated moves to set up a gene therapy laboratory. The technology was acquired with the help of scientists from the Salk Institute, San Diego, Unite d States, and the Human Gene Therapy Research Institute, Iowa, U.S. Dr. Bhisey said: "We were the first laboratory in India to initiate pre-clinical studies for gene therapy in cancer using the 'suicide' gene strategy." The work on gene therapy is funded by the Union Government's Department of Biotechnology.

Conventional therapies for cancer are radiotherapy (using X-rays, cobalt, and so on) and chemotherapy (drugs). Gene therapy is in the trial stage. Dr. Bhisey said that after pre-clinical trials, the CRI would start clinical trials. There were protocols i nvolved in this. Permission from statutory authorities had to be obtained before the trials began, he said.

The CRI is now located on the premises of the Tata Memorial Hospital at Parel in Mumbai. The ACTREC, of which the CRI will form a part, has spacious premises. The ACTREC will provide modern facilities for cancer research. While the CRI now occupies only 3,400 square metres, the ACTREC will have 11,448 sq m at its disposal. The entire premises occupy an area of 24 hectares. In the first phase, the CRI at ACTREC will have a main block, an animal house with modern facilities, and sections for cell biology, biological chemistry, immunology, carcinogenesis, chemotherapy, neuro-oncology, cell and developmental pathology and epidemiology.