Sulforaphane modulates the expression of Cyp6a2 and Cyp6g1 in larvae of the ST and HB crosses of the Drosophila wing spot test and is genotoxic in the ST cross.
Constitutive overexpression of Cyp6g1 and Cyp6a2 genes in DDT-resistant line Oregon-flare of the Drosophila melanogaster wing spot test (SMART) has been reported. Cyp6g1 and Cyp6a2 expression levels were compared against the β-actin gene in the standard (ST) and high bioactivation (HB) crosses of the Somatic Mutation and Recombination test (SMART) treated with sulforaphane or phenobarbital as the control inductor. The CYP450s' enzymatic activity was determined by overall NADH consumption. The expression levels of both genes and the CYP450s activity was higher in the HB cross. The Cyp6g1 levels were higher than those of Cyp6a2 in both crosses, but lower than the expression of β-actin. Sulforaphane decreased Cyp6g1 in the HB cross and increased it in the ST cross; Cyp6a2 expression was inhibited in the ST cross. Sulforaphane resulted mutagenic in the ST cross, which could be related to the inhibition of Cyp6a2. Phenobarbital did not modify the Cyp6g1 levels but increased the Cyp6a2 and CYP450s basal activity. Although the transcript levels were always higher in the HB cross than in the ST, the expression of Cyp6a2 and Cyp6g1 was not constitutive and was independent one from the other. Sulforaphane modulated both genes in a differential way in each cross and, in contrast to its putative protective effect, it resulted to be mutagenic.
Vázquez-Gómez
G
G
Genetic Toxicology, Biology, UBIPRO, FES Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, Mexico.
Sánchez-Santos
A
A
Vázquez-Medrano
J
J
Quintanar-Zúñiga
R
R
Monsalvo-Reyes
A C
AC
Piedra-Ibarra
E
E
Dueñas-García
I E
IE
Castañeda-Partida
L
L
Graf
U
U
Heres-Pulido
M E
ME
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000633:toxicity; D003433:Crosses, Genetic; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D000072472:Cytochrome P450 Family 6; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D005822:Genetic Vectors; D006993:Hypnotics and Sedatives / Q000633:toxicity; D017879:Isothiocyanates; D007814:Larva / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009243:NAD / Q000378:metabolism; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000235:genetics; D010634:Phenobarbital / Q000633:toxicity; D011995:Recombination, Genetic / Q000235:genetics; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology* / Q000633:toxicity; D014921:Wings, Animal / Q000033:anatomy & histology*
D000199:Actins; D016588:Anticarcinogenic Agents; D029721:Drosophila Proteins; D006993:Hypnotics and Sedatives; D017879:Isothiocyanates; D009153:Mutagens; D009841:Oligonucleotides; D013454:Sulfoxides; D013861:Thiocyanates; D009243:NAD; D003577:Cytochrome P-450 Enzyme System; C446928:Cyp6g1 protein, Drosophila; C109499:Cyp6a2 protein, Drosophila; D000072472:Cytochrome P450 Family 6; C016766:sulforaphane; D010634:Phenobarbital