CORRESPONDENCE

Re: Benzo[a]pyrene Diol Epoxide and Bleomycin Sensitivity and Susceptibility to Cancer of Upper Aerodigestive Tract

Armen K. Nersesyan

Affiliation of author: Laboratory of Carcinogenesis, Cancer Research Centre, 76 Fanardjian Street, Yerevan, Armenia

Correspondence to: Armen K. Nersesyan, Ph.D., D.Sc., 1 Tigran Mets Avenue, Apt. 4, Yerevan 375010, Armenia (e-mail: genetik{at}ysu.am).

Wu et al. (1) have based their studies on the assay of Hsu et al. (2) who developed the bleomycin sensitivity assay in which the number of chromatid breaks induced by in vitro exposure to bleomycin in short-term cultures of peripheral blood lymphocytes was assessed to estimate host susceptibility to neoplastic cell transformation. Wu et al. (1) investigated the susceptibility to bleomycin and benzo[a]pyrene diol epoxide of chromosomes of lymphocytes from subjects who were previously treated with surgery, radiotherapy, or both for stage I or II squamous cell carcinoma of the head and neck and from healthy subjects. They concluded that the people who were sensitive to both mutagens were at 19.2-fold increased risk of cancer of the upper aerodigestive tract. In my opinion, Hsu's hypothesis is not applicable in all cases. Indeed, both the ataxia-telangiectasia (AT) heterozygotes and the homozygotes are cancer prone. Only about 10%-20% of homozygotes develop neoplasms, mostly lymphomas and leukemias. Retrospective studies have indicated a substantial increase in all cancers for AT heterozygotes. But chromosomes of homozygote individuals are very sensitive to mutagens, whereas those of the heterozygotes are not (3). Recent investigations have shown that bleomycin was much less effective in inducing DNA damage in leukocytes from children with thyroid cancer than those from healthy subjects (4). Therefore, the sensitivity of lymphocytes of subjects to bleomycin is not a good predictor of high risk of cancer in all cases.

The authors have used the term "clastogenic" to include both mutagenic and carcinogenic effects. But the term clastogenic means chromosome damaging.

Wu et al. (1) have noted that the frequencies of spontaneous chromatid breaks are extremely low in normal subjects and in case patients. But Hastak et al. (5) have shown that patients with precancerous oral lesions, e.g., oral submucous fibrosis, oral leukoplakia, and oral lichen planus, showed an increase in the number of micronuclei in circulating lymphocytes. The authors also showed that benzo[a]pyrene can induce a substantially increased level of micronuclei in lymphocytes of patients compared with those in the healthy subjects. But can we assume from these findings that these patients are at high risk for lung cancer? Moreover, some investigators (6) suggest that an increased level of chromosomal aberrations in peripheral lymphocytes reflects an enhanced cancer risk (e.g., only the spontaneous breaks, but not bleomycin-induced breaks, in cells of workers exposed to different carcinogens or mutagens). Studies in Nordic and Italian cohorts have shown that the standardized incidence ratio for all cancers is elevated among subjects with a high frequency of chromosomal aberrations. These investigators conclude that the frequency of chromosomal aberrations in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans. So, there are two contradictory ideas for prediction of cancer susceptibility based on 1) mutagen-induced chromosomal breaks or 2) spontaneous chromosomal breaks. But, in my opinion, the conclusion would be more realistic if they are supported by the cancer incidence data.

In conclusion, the data presented by Wu et al. (1) concerning the calculation of risk of cancer of upper aerodigestive tract in subjects sensitive to mutagens are hypothetical; and only future prospective investigations will show whether conclusions of their paper have practical significance.

REFERENCES

1 Wu X, Gu J, Hong WK, Lee JJ, Amos CI, Jiang H, et al. Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract. J Natl Cancer Inst 1998;90:1393-99.[Abstract/Free Full Text]

2 Hsu TC, Johnston DA, Cherry LM, Ramkissoon D, Schantz SP, Jessup JM, et al. Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis. Int J Cancer 1989;43:403-9.[Medline]

3 Tomanin R, Sarto F, Mazzotti D, Giacomelli L, Raimondi F, Trevisan C. Louis-Bar syndrome: spontaneous and induced chromosomal aberrations in lymphocytes and micronuclei in lymphocytes, oral mucosa and hair root cells. Hum Genet 1990;85:31-8.[Medline]

4 Frenzilli G, Lori A, Panasiuk G, Ferdeghini M, Barale R. Comet assay on children's leukocytes 8 years after the Chernobyl disaster. Mutat Res 1998;415:151-8.[Medline]

5 Hastak K, Lubri N, Jakhi SD, More C, John A, Ghaisas SD, et al. Effect of turmeric oil and turmeric oleorisin on cytogenetic damage in patients suffering from oral submucous fibrosis. Cancer Lett 1997;116:265-9.[Medline]

6 Hagmar L, Bonassi S, Stromberg U, Brogger A, Knudsen LE, Norppa H, et al. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res 1998;58:4117-21.[Abstract]



             
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