233- Chemical carcinogenesis

Question 1

mutagen vs non-mutagen carcinogens

Answer 1

mutagen: genotoxic. Directly bind to DNA or are pro-carcinogens (most carcinogens) which must be activated
Non-mutagen: nongenotoxic. mitogenic, cytotoxic, receptor-mediated

In which category do most carcinogens fit?

Question 2

describe the ames test: what do you do? what is the fundamental assumption?

Answer 2

You add a suspected carcinogen to agar with salmonella which requires Histidine from environment to grow. Add rat liver to activate if needed. If bacteria grow they have mutated. Assumes that if a substance in mutagenic it is carcinogenic (not always true)

Question 3

Hepatocyte DNA repair assay: why is it useful? what does it do?

Answer 3

more accurately reflects human metabolism than Ames test using rat liver. Mutated DNA takes up radiolabeled thymidine during the excision repair process

Question 4

Who grading for carcinogenicity? EPA grading?

Answer 4

1: carcinogenic, 2A: probably, 2B: possibly, 3: not sure, 4: probably not

Same as above except A-E

Question 5

three stages of carcinogenesis: which are reversible?

Answer 5

Initiation: irreversible initial damage to DNA
Promotion: reversible (initially) clonal expansion of initiated cell by a PROMOTER when applied REPEATEDLY
Progression: irreversible conversion of benign condition to malignant one (“progression 2” leads to ability to metastasize)

Question 6

How would you study tumor initiation as well as promotion

Answer 6

multi-stage mouse