Question

The compound benzo[a]pyrene is found in cigarette smoke. This compound chemically modifies guanine bases in DNA. Such abnormal bases are typically removed by an enzyme that hydrolyzes the base, leaving an apurinic site. If such a site is left unrepaired, an adenine is preferentially inserted across from the apurinic site. In a landmark paper on lung cancer patients (Harris et al (1991) Nature 350: 377-378) 15 out of 25 patients had a G-T transversion in the p53 gene, which has a known role in cancer formation. You are testifying as an expert witness in a court case where the widow of the man who was a lifelong smoker and died of lung cancer is suing a company for manufacturing the tobacco products that killed her husband. What would you tell the jury?

Answer 1

I would tell that benzo(a) pyrene metabolites are mutagenic and highly carcinogenic and it is listed as group 1 carcinogen by IARC.

X ray crystallographic and NMR structure studies have shown how this binding damages the DNA by confusing the double helical structure. This disrupts thenormal process of copying DNA and causes mutation.

It targets p53 gene, which is a transcription factor that regulates cell cycle and functions as tumor suppressor.

By inducing guanine to thymine transversion within p53, there is a probability that benzo(a) pyrene inactivates the tumor suppression ability in certain cells, leading to cancer.

Thus, it is the sole responsibility of the tobacco manufacturing company that produces such products which are life threatning and causes death of many people. Such companies should be banned from manufacturing carcinogenic substances.