Page 158 - Concise Pathology for Exam Preparation ( PDFDrive )

6 Neoplasia 143

(c) Naturally occurring products
(i) Aflatoxin B 1 (role in pathogenesis of hepatocellular carcinoma)
(ii) Cycasin (role in hepatobiliary tumours)
(iii) Safrole (carcinogenic and genotoxic)
(iv) Betel nuts (oral cancer)
(d) Miscellaneous
(i) Nitrosamines and amides (role in pathogenesis of gastric carcinoma)
(ii) Vinyl chloride monomer (implicated in the pathogenesis of angiosarcoma of liver)
(iii) Asbestosis (may lead to bronchogenic carcinoma and mesothelioma)
(iv) Nickel, lead, cobalt and chromium (cause epidermal hyperplasia and basal
cell carcinoma)
Stages of chemical carcinogenesis are shown in Flowchart 6.7.

Procarcinogen Biotransformation of procarcinogen in
endoplasmic reticulum of hepatocytes by
mono-oxygenases of cytochrome P-450
Carcinogen

Conversion into electron-deficient electrophiles
Initiation Binding of electrophiles to electron-rich portions of cell

(DNA, RNA and proteins; target molecule chiefly DNA)

• Permanent DNA damage, leading to initiation of cell
• Altered cell undergoes at least one cycle of proliferation
in order to transfer the change to the progeny
Promotion Clonal proliferation of altered cell

Neoplasm
FLOWCHART 6.7. Stages of chemical carcinogenesis.

The contrasting features of initiators and promoters are listed in Table 6.7.

TABLE 6.7. Contrasting features of initiators and promoters
Features Initiators Promoters
Sequence of Applied first Applied after initiator
application
Mechanism Induction of mutation Not mutagenic; instead are mitogenic
Induce cell cycling and reinforce the action of
initiators rather than inducing a mutation
Dose Single for a short time Repeated over a long time
Response Sudden Delayed
Molecular change Initiation causes irreversible changes and Promoters induce reversible changes
has memory
Examples Most chemical carcinogens, radiation Hormones, phorbol esters

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