Infectious Theory of Carcinogenesis
The infectious theory was pioneered by the oncologist L.A. Zilber. His concept proposed that certain neoplasms arise due to the action of specific oncogenic viruses.
The evidence base was built over decades. A critical milestone was achieved in experiments where cell-free filtrates of tumor tissue were injected into healthy recipient animals, inducing the development of neoplasms.
- In 1908, researchers first successfully induced leukemia in chickens experimentally.
- In 1911, P. Rous described the first oncogenic filterable agent—the Rous sarcoma virus.
- In 1976, the first gene triggering malignant transformation—the src oncogene—was discovered within this retrovirus. Today, science knows of over 100 such viral oncogenes.
DNA Oncoviruses
The genetic apparatus of DNA oncoviruses includes two groups of genes: those responsible for replication and those encoding structural viral proteins.
Their mechanism of action relies on complete or partial integration into the host cell genome. However, malignant transformation occurs extremely rarely (approximately one in a million cases). This is because for a tumor to develop, the virus must infect a susceptible cell without killing it. In the vast majority of cases, infection ends in lysis—cell death due to membrane destruction upon the release of new viral progeny. Consequently, DNA viruses much more frequently cause conventional infectious diseases rather than tumor growth.
This group includes:
- Epstein-Barr virus: Associated with endemic (African) Burkitt lymphoma and nasopharyngeal carcinoma.
- Human papillomavirus: Causes papillomas, skin, and anogenital cancers.
- Adenoviruses, Hepatitis B virus, and Herpesviridae (including the varicella-zoster virus).
RNA Oncoviruses (Retroviruses)
RNA oncoviruses belong to the retrovirus family. Unlike their DNA counterparts, they rarely cause acute infections (with the exception of HIV and Hepatitis C) and are capable of persisting asymptomatically in the body for years.
Their genome consists of three core gene groups:
- gag — encodes the structural proteins of the virus.
- pol — responsible for the synthesis of reverse transcriptase. This enzyme creates viral DNA based on an RNA template for subsequent integration into the host genome.
- env — encodes the viral envelope glycoproteins.
RNA viruses are highly efficient agents of malignant transformation. The reason lies in the fact that they exit the cell without destroying its membrane. The cell survives and gives rise to sarcomas, leukemias, or solid tumors (e.g., the RNA virus HTLV-1 causes certain types of T-cell leukemias and lymphomas).
Microbial Carcinogenesis
Tumors can be triggered not only by viruses but also by bacteria. A classic example is Helicobacter pylori, which inhabits the acidic environment of the gastric mucosa. It is a proven etiological factor for gastric adenocarcinoma and MALT lymphoma.
Pathogenesis of Lymphoma Development:
- Chronic Helicobacter pylori infection recruits reactive T lymphocytes to the tissue.
- T cells begin actively producing cytokines.
- Cytokines stimulate uncontrolled proliferation of B lymphocytes.
- Mutations accumulate in actively dividing B cells, leading to malignant transformation.
- Tumor growth acquires a monoclonal character and escapes T-cell regulation.
Polyetiological Theory
Modern science integrates all existing perspectives into a unified polyetiological theory. It states that tumors are a heterogeneous group of diseases in which multiple etiological factors may participate, and their effects can be additive and synergistic.
The primary mechanism of carcinogenesis is the occurrence of mutations in somatic cells due to DNA damage caused by carcinogens. The mutational nature is supported by strict correlations between chromosomal abnormalities and specific tumor types, as well as the fact that transfection (transfer) of viral oncogenes into normal cells inevitably leads to a tumor phenotype.