Genotoxicity (mitotic recombination) of the cancer chemotherapeutic agents cisplatin and cytosine arabinoside in Aspergillus nidulans.
Cisplatin (cis-diamminedichloroplatinum, cis-DDP) and cytosine arabinoside (ara-C) are anticancer drugs used in the treatment of human cancer. The two chemotherapeutic drugs were tested in current research for their recombinogenic potential in diploid cells of Aspergillus nidulans. Non-cytotoxic concentrations of ara-C (0.4 and 0.8 microM) and cis-DDP (1.5, 3.0 and 6.0 microM) were strong recombinagens in A. nidulans UT448//A757 diploid strain, which induced homozygosis of recessive genetic markers, previously present in heterozygous condition. Drugs significantly increased homozygosity index (HI) values for five nutritional genetic markers when compared with those determined in the absence of anticancer drugs. Since mitotic recombination is a mechanism leading to malignant growth through loss of heterozygosity at tumor-suppressor loci, ara-C and cis-DDP may be characterized as secondary promoters of malignant neoplasia in diagnosed cancer patients, after chemotherapy treatment.
Miyamoto
C T
CT
Universidade Estadual de Maringá, Departamento de Biologia Celular e Genética, Avenida Colombo 5790, Maringá, Paraná 87020-900, Brazil.
Sant'Anna
J R
JR
Franco
C C S
CC
Castro-Prado
M A A
MA
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000970:Antineoplastic Agents / Q000633:toxicity*; D001233:Aspergillus nidulans / Q000187:drug effects* / Q000235:genetics; D001710:Biotin / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003561:Cytarabine / Q000633:toxicity*; D006801:Humans; D019656:Loss of Heterozygosity; D008715:Methionine / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D011736:Pyridoxine / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects*; D012256:Riboflavin / Q000378:metabolism
D000970:Antineoplastic Agents; D003561:Cytarabine; D001710:Biotin; D008715:Methionine; D011736:Pyridoxine; D002945:Cisplatin; D010129:4-Aminobenzoic Acid; D012256:Riboflavin