Rat lung cancer induced by malathion and estrogen.
Lung cancer can originate from exposure to exogenous and endogenous environmental carcinogens. The use of organophosphorus insecticides has significantly increased in agricultural environments and in urban settings. There is evidence that estrogen can increase lung cancer risk in women. The aim of the present study was to analyze morphological and molecular alterations induced by malathion (M) and 17beta-estradiol (E2) in rat lung tissues. There were four groups: saline solution (control) (100 microg/100 g body weight; BW), M (22 mg/100 g BW), E2 (30 microg/100 gr BW) and combination of both. The animals were injected over a 5-day period and sacrificed 240 days after treatments and lung tissues were excised and analyzed for morphological alterations. Morphometric analysis indicated that M plus E2-treated animals showed a significantly (P<0.05) higher incidence of parenchyma with alveolar proliferative lesions (PAPL), preneoplastic lesions in bronchiolar epithelium (hyperplasia, metaplasia, carcinoma in situ and invasive carcinoma) and atypical lymphatic morphology (lymphatic cell aggregates; LCA) than M or E2 alone-treated and control animals after 240 days. Molecular biology studies indicated that c-ErbB2 and Rho-A had higher protein expression in M plus E2-treated animals in comparison to control and either M- or E-treated animals. In summary, the combination of M and E2 sharply induced pathological lesions in lung alveolar parenchyma, bronchiolar epithelia and lymphatic tissues, in comparison to control animals or in animals treated with either substance alone. These results indicated an increase in risk of rodent lung tumor formation by environmental and endogenous substances.
Echiburú-Chau
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Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.
Calaf
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GM
D000818:Animals; D004958:Estradiol / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D008294:Malathion / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000187:drug effects
D004958:Estradiol; D004967:Estrogens; D007306:Insecticides; D008294:Malathion; D018719:Erb-b2 Receptor Tyrosine Kinases; D020742:rhoA GTP-Binding Protein