Page 363 - Industrial Ventilation Design Guidebook

5.3 TOX1CITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 3 I 9

proto-oncogene to an oncogene, which then amplifies the carcinogenic pro-
cess. On the other hand, mutations that inactivate tumor suppressor genes also
greatly amplify carcinogenesis induced by exposure to chemical com-
187 188
pounds. ' In fact, inactivating mutations in tumor suppressor genes may
be vital for the initiation and progression of the carcinogenic process. For ex-
ample, mutations of ras-, raf-, jun-, fur-, and myc-oncogenes are known to be
189
crucial in the development of lung cancer. Table 5.22 lists important onco-
genes and tumor suppressor genes that may be involved in human carcinogen-
esis.
A few tumor suppressor genes have also been identified. The most impor-
tant of these are the p53 tumor suppressor gene and the retinoblastoma
gene. 190 When functioning normally, the p53 tumor suppressor gene will stop
cell division after DNA damage to give the cell time to repair the damage. In-
activating mutations in the p53 tumor suppressor gene may, therefore, amplify
carcinogenesis by preventing the cell from repairing damage to its genetic ma-
terial. In fact, mutations of p53 tumor suppressor gene are the most usual ge-
netic changes in human cancers, and it seems that some chemical carcinogens

TABLE 5.22 Important Oncogenes and Tumor Suppressor Genes in
Human Cancers

Tissues associated with the cancer
Oncogene
ras Lung, colon, pancreas
rat Lung
jun Lung
erb-Bl(neu) Breast, lung
fur Lung
myb Lung
myc Bone marrow (acute leukemia)
Lymphatic tissue (Burkitt lymphoma), lung
Nervous tissue (neuroblastoma)
abl Bone marrow

Tumor suppressor gene
Rb Retina (retinoblastoma), lung
p53 Lung, urinary bladder, intestine, breast
WT-1 Kidney (Wilms' tumor)
APC Colon
DCC Colon
BRCA Breast
HNPCC Colon
Source: Modified from Va'ha'kangas and Savolainen. 179