Page 232 - Textbook of Pathology, 6th Edition

216

SECTION I

Figure 8.21 Schematic representation of activation-inactivation of cancer-associated genes in cell cycle.
General Pathology and Basic Techniques
sequence in development of colorectal carcinoma. Recent by two Japanese workers (Yamagiwa and Ichikawa) in 1914
studies on human genome in cancers of breast and colon have in the rabbit’s skin by repeatedly painting with coal tar. Since
revealed that there is a multistep phenomenon of then the list of chemical carcinogens which can experi-
carcinogenesis at molecular level; on an average a malignant mentally induce cancer in animals and have epidemiological
tumour has large number of genetic mutations in cancers. evidence in causing human neoplasia, is ever increasing.
10. MICRORNAs IN CANCER: ONCOMIRS
Stages in Chemical Carcinogenesis
MicroRNAs (miRNAs) are evolutionally conserved,
endogenous, noncoding single stranded RNA molecules with The induction of cancer by chemical carcinogens occurs after
a length of 22 nucleotides only. Normally, miRNAs function a delay—weeks to months in the case of experimental
as the posttranslational gene regulators of cell proliferation, animals, and often several years in man. Other factors that
differentiation and survival. More than 500 miRNAs have influence the induction of cancer are the dose and mode of
been identified. Recent evidence indicates that miRNAs have administration of carcinogenic chemical, individual
an oncogenic role in initiation and progression of cancer and susceptibility and various predisposing factors.
are termed as oncogenic microRNAs, abbreviated as Basic mechanism of chemical carcinogenesis is by
oncomiRs. In combination with other tumour associated induction of mutation in the proto-oncogenes and anti-
genes, oncomiRs can perform various functions: as tumour oncogenes. The phenomena of cellular transformation by
suppressor, as tumour promoter, and as pro-apoptotic. chemical carcinogens (as also other carcinogens) is a progres-
The above properties of cancer cells are schematically sive process involving 3 sequential stages: initiation,
illustrated in Fig. 8.21. promotion and progression (Fig. 8.22).
B. CHEMICAL CARCINOGENESIS 1. INITIATION OF CARCINOGENESIS
The first ever evidence of any cause for neoplasia came from Initiation is the first stage in carcinogenesis induced by
the observation of Sir Percival Pott in 1775 that there was initiator chemical carcinogens. The change can be produced
higher incidence of cancer of the scrotum in chimney-sweeps by a single dose of the initiating agent for a short time, though
in London than in the general population. This invoked wide larger dose for longer duration is more effective. The change
interest in soot and coal tar as possible carcinogenic agent so induced is sudden, irreversible and permanent. Chemical
and the possibility of other occupational cancers. The first carcinogens acting as initiators of carcinogenesis can be
successful experimental induction of cancer was produced grouped into 2 categories (Table 8.7):